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Study Evaluating 13 Valent Pneumococcal Conjugate Vaccine With Trivalent Inactivated Influenza Vaccine

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00521586
Collaborator
(none)
1,116
Enrollment
41
Locations
2
Arms
75
Duration (Months)
27.2
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, tolerability and immune response when 13-valent pneumococcal conjugate vaccine (13vPnC) and the trivalent inactivated flu vaccine (TIV) are given together to healthy adults aged 50-59 years who are naive to 23-valent pneumococcal polysaccharide vaccine (23vPS), or when the vaccines are given 1 month apart. It will also evaluate the immune response to 13vPnC once per year for 4 years and then to a second dose of 13vPnC given 5 years after the first dose.

Condition or Disease Intervention/Treatment Phase
  • Biological: 13 valent pneumococcal conjugate vaccine
  • Biological: 13 valent pneumococcal conjugate vaccine
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1116 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase 3, Randomized, Double-blind Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of A 13-valent Pneumococcal Conjugate Vaccine (13vpnc) When Administered Concomitantly With Trivalent Inactivated Influenza Vaccine In Healthy Adults 50-59 Years Of Age Who Are Naive To 23-valent Pneumococcal Polysaccharide Vaccine And To Evaluate The Immune Response Of A Second Dose Of 13vpnc Administered 5 Years After Initial 13vpnc Vaccination
Study Start Date :
Sep 1, 2007
Actual Primary Completion Date :
Dec 1, 2013
Actual Study Completion Date :
Dec 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Other: 1

arm 1 = TIV +13vPnC at visit 1, placebo at visit 2 then 13vPnC at year 5

Biological: 13 valent pneumococcal conjugate vaccine
TIV +13vPnC at dose 1 placebo at dose 2, one month after dose 1 13vPnC at year 5
Other Names:
  • 0.5 mL dose of TIV and 13vPnC at dose 1, 0.5 mL dose of of placebo at dose 2, and 0.5ml dose of 13vPnC at year 5 will be administered into left deltoid muscle

    		•
    Other: 2

    arm 2 = TIV + placebo at visit 1, then 13vPnC at visit 2 and at year 5

    Biological: 13 valent pneumococcal conjugate vaccine
    TIV + placebo at dose 1 13vPnC at dose 2, one month after dose 1 and 13vPnC at year 5
    Other Names:
  • 0.5 mL dose of TIV and of placebo at dose 1 and 0.5 mL dose of 13vPnC at dose 2 and year 5 will be administered into left deltoid muscle

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving at Least 4-fold Increase in Titer for Concomitant Trivalent Inactivated Influenza Vaccine (TIV) Antigens 1 Month After Dose 1 [1 month after Dose 1]

      Percentage of participants achieving at least 4-fold increase in titer for concomitant Trivalent Inactivated Influenza Vaccine (TIV) were measured by standard Hemagglutination Inhibition Assay (HAI) for the A/H1, A/H3, and B vaccine strains.Exact, unconditional, 2-sided, 95% confidence intervals (CI) on the difference in proportions (13vPnC+TIV - Placebo+TIV) was calculated. N(number of participants analyzed)=participants with a determinate antibody titer to the given concomitant vaccine antigen. n=participants who met the prespecified level for the given antigen.

    2. Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose [1 month after 13vPnC Dose at year 0]

      Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose at year 0 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.

    Other Outcome Measures

    1. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Month After 13vPnC (Year 5) [1 month after 13vPnC (Year 5)]

      Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 Month After 13vPnC (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

    2. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) Before 13vPnC (Year 5) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5)]

      Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants with immunogenicity data at both Year 5 endpoints.

    3. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold-Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 5) [before 13vPnC (Year 5), 1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before 13vPnC (Year 5) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. n=participants with valid and determinate assay results for the specified serotype from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    4. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.n=participants with valid and determinate assay results for the specified serotype for both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    5. Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to 1 Month After 13vPnC (Year 0) [1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    6. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) Before 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5)]

      Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.

    7. Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 0) [before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before13vPnC (Year 0) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    8. Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) Before and 1 Month After 13vPnC (Year 0), 1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) [Before,1 month after 13vPnC (Year 0), 1, 2, 3, 4 years after initial vaccination (Year 0); before,1 month after 13vPnC (Year 5)]

      Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before, 1 month after 13vPnC (Year 0), at Years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. n=participants with valid and determinate assay results for the specified serotype at before, 1 month after 13vPnC (Year 0), at Years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) blood draws.

    9. Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC (Year 0),1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) Relative to Before 13vPnC (Year 0) [Before, 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before to 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both the baseline and the various time points.

    10. Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) 1 Month After 13vPnC (Year 5) [1 month after 13vPnC (Year 5)]

      Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 1 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.

    11. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) Before 13vPnC (Year 5) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5)]

      Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both Year 5 time points.

    12. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 5) [before 13vPnC (Year 5), 1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before 13vPnC (Year 5) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    13. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) 1 Month After 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points

    14. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to 1 Month After 13vPnC (Year 0) [1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    15. Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) Before 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5) [before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5)]

      Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.

    16. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 0) [Before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from Before 13vPnC (Year 0) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.

    17. Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Before and 1 Month After 13vPnC (Year 0), 1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) [Before,1 month after 13vPnC (Year 0), 1, 2, 3, 4 years after initial vaccination (Year 0); before,1 month after 13vPnC (Year 5)]

      Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1(Dose1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1(Dose 1, placebo+TIV). Placebo matched to 13vPnC was administered 1 month after(Dose 2, placebo), or 13vPnC was administered 1 month after (Dose 2, 13vPnC).Participants were further followed-up for 1 month,then attended a 6-month follow-up visit for safety.Participants were then followed-up yearly for 4 years.Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination.Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.

    18. Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC (Year 0),1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) Relative to Before 13vPnC (Year 0) [Before, 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5)]

      GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before to 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both the baseline and the various time points.

    19. Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After Dose 1 (Year 0) [Within 14 days after Dose 1 (Year 0)]

      Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder). Local reactions were measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.

    20. Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After Dose 2 (Year 0) [Within 14 days after Dose 2 (Year 0)]

      Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder). Local reactions were measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.

    21. Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After 13vPnC (Year 5) [Within 14 days after 13vPnC (Year 5)]

      Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder).

    22. Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After Dose 1 (Year 0) [Within 14 days after Dose 1 (Year 0)]

      Percentage of participants who experienced specific systemic events (mild: 38.0 to 38.4 degrees Celsius [C], moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening greater than [>] 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.

    23. Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After Dose 2 (Year 0) [Within 14 days after Dose 2 (Year 0)]

      Percentage of participants who experienced specific systemic events (absent: 38.0 degrees Celsius [C], mild: 38.0 to 38.4 degrees C, moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening > 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.

    24. Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After 13vPnC (Year 5) [Within 14 days after 13vPnC (Year 5)]

      Percentage of participants who experienced specific systemic events (Fever: >= 38.0 degrees Celsius [C], mild: 38.0 to 38.4 degrees C, moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening > 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.

    25. Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After Dose 1 (Year 0) [Within 30 Minutes After Dose 1 (Year 0)]

      Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity). Acute pain was measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.

    26. Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After Dose 2 (Year 0) [Within 30 Minutes After Dose 2 (Year 0)]

      Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity). Acute pain was measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.

    27. Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After 13vPnC (Year 5) [Within 30 Minutes After 13vPnC (Year 5)]

      Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity).

    28. Percentage of Participants With Serious Adverse Events (SAEs) or Non-serious Adverse Events (Non-SAEs) [Signing of informed consent up to 194 days after re-vaccination at Year 5]

      AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Non-serious AEs are AEs excluding SAEs. In Years 1-4, only deaths and withdrawals due to AEs or SAEs were to be recorded in the case report form.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 59 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Male or female aged 50 to 59 years

    • Determined by medical history, physical examination and clinical judgement to be eligible for the study

    • Able to complete electronic diary

    • Available for the 5 year 9 month duration of the study

    Exclusion Criteria:

    • Previous vaccination with any licensed or experimental pneumococcal vaccine

    • Allergic to egg proteins and chicken proteins

    • History of Guillian-Barre syndrome

    • Vaccination with TIV within 6 months before study start

    • Vaccination with diphtheria-containing vaccine within 6 months of study start

    • Serious chronic disorders including immunodeficiency or metastatic malignancy

    • Known or suspected hypersensitivity to any vaccine or vaccine component

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Research Advantage, Inc. Chandler Arizona United States 85224
    2 Peninsula Research Associates Rolling Hills Estates California United States 90274
    3 Clinical Trials Center Pediatric Infectious Diseases and Clinical Trials Aurora Colorado United States 80045-7144
    4 Tampa Bay Medical Research, Inc. Clearwater Florida United States 33761
    5 A. G. A. Clinical Trials Hialeah Florida United States 33012
    6 Advanced Clinical Research Meridian Idaho United States 83642
    7 Accelovance Peoria Illinois United States 61602
    8 Suite 100 Riverdale Maryland United States 20737
    9 Mayo Clinic Rochester Minnesota United States 55905
    10 Radiant Research, Inc St. Louis Missouri United States 63141
    11 Big Sky Clinical Research Butte Montana United States 59701
    12 FFM Clinical Research Camillus New York United States 13031
    13 Rochester Clinical Research Rochester New York United States 14609
    14 University of Rochester Medical Center Rochester New York United States 14642
    15 PMG Research of Raleigh, LLC Cary North Carolina United States 27518
    16 Hickory Family Practice Associates Hickory North Carolina United States 28601
    17 PMG Research of Hickory, LLC Hickory North Carolina United States 28601
    18 Unifour Medical Research Associates, LLC Hickory North Carolina United States 28601
    19 Unifour Medical Research Associates Hickory North Carolina United States 28601
    20 Fairbrook Medical Clinic Hickory North Carolina United States 28602
    21 PMG Research of Hickory, LLC Hickory North Carolina United States 28602
    22 Unifour Medical Research Associates, LLC Hickory North Carolina United States 28602
    23 PMG Research of Raleigh, LLC Raleigh North Carolina United States 27609
    24 PMG Research of Salisbury Salisbury North Carolina United States 28144
    25 PMG Research of Winston-Salem Winston-Salem North Carolina United States 27103
    26 Cincinnati Children's Hospital Medical Center Gamble Program for Clinical Studies Cincinnati Ohio United States 45206
    27 Rapid Medical Research, Inc. Cleveland Ohio United States 44122
    28 Prestige Clinical Research Franklin Ohio United States 45005
    29 Preferred Primary Care Physicians, Inc Carnegie Pennsylvania United States 15106
    30 Family Healthcare Partners Grove City Pennsylvania United States 16127
    31 Family Practice Medical Associates South, Jefferson Office Jefferson Hills Pennsylvania United States 15025
    32 Kid's Plus Pediatrics Pittsburgh Pennsylvania United States 15217
    33 Primary Physicians Research Inc. Pittsburgh Pennsylvania United States 15241
    34 Family Practice Medical Associates South Upper St. Clair Pennsylvania United States 15241
    35 The Washington Hospital Family Medicine Washington Pennsylvania United States 15301
    36 Internal Medicine & Pediatric Associates of Bristol, PC Bristol Tennessee United States 37620
    37 PMG Research of Bristol, LLC Bristol Tennessee United States 37620
    38 Volunteer Research Group Knoxville Tennessee United States 37920
    39 Clark D. McKeever, M.D. Research for Health Houston Texas United States 77055-6040
    40 Diagnostics Research Group San Antonio Texas United States 78229
    41 Advanced Clinical Research West Jordan Utah United States 84088

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00521586
    Other Study ID Numbers:
    • 6115A1-3001
    • B1851020
    First Posted:
    Aug 28, 2007
    Last Update Posted:
    Apr 9, 2015
    Last Verified:
    Apr 1, 2015
    Keywords provided by Pfizer
    Pneumococcal Conjugate Vaccine
    Additional relevant MeSH terms:
    Influenza, Human
    Vaccines
    Heptavalent Pneumococcal Conjugate Vaccine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Initially 1060 participants were reported to complete the 6 month follow up at Year 0, however 6 additional participants who were reported to have withdrawn initially, actually completed the 6 month follow up at Year 0.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Period Title: Initial Vaccination (Year 0)
    STARTED 554 562
    Vaccinated Dose 1 551 560
    Vaccinated Dose 2 538 543
    Initially Reported to Complete Year 0 531 529
    COMPLETED 533 533
    NOT COMPLETED 21 29
    Period Title: Initial Vaccination (Year 0)
    STARTED 533 533
    COMPLETED 364 363
    NOT COMPLETED 169 170
    Period Title: Initial Vaccination (Year 0)
    STARTED 364 363
    Vaccinated 13vPnC (Year 5) 364 363
    Completed 1 Month Follow-up 363 359
    Completed 6 Month Follow-up 361 351
    COMPLETED 361 351
    NOT COMPLETED 3 12

    Baseline Characteristics

    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) Total
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Total of all reporting groups
    Overall Participants 551 560 1111
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.6
    (2.8)
    54.6
    (2.9)
    54.6
    (2.8)
    Sex: Female, Male (Count of Participants)
    Female
    319
    57.9%
    322
    57.5%
    641
    57.7%
    Male
    232
    42.1%
    238
    42.5%
    470
    42.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving at Least 4-fold Increase in Titer for Concomitant Trivalent Inactivated Influenza Vaccine (TIV) Antigens 1 Month After Dose 1
    Description Percentage of participants achieving at least 4-fold increase in titer for concomitant Trivalent Inactivated Influenza Vaccine (TIV) were measured by standard Hemagglutination Inhibition Assay (HAI) for the A/H1, A/H3, and B vaccine strains.Exact, unconditional, 2-sided, 95% confidence intervals (CI) on the difference in proportions (13vPnC+TIV - Placebo+TIV) was calculated. N(number of participants analyzed)=participants with a determinate antibody titer to the given concomitant vaccine antigen. n=participants who met the prespecified level for the given antigen.
    Time Frame 1 month after Dose 1

    Outcome Measure Data

    Analysis Population Description
    Evaluable immunogenicity population:eligible participants who received vaccination as assigned;had blood drawn within pre-specified time-frames;had at least 1 valid,determinate assay result;had no major protocol violation.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 530 531
    A/H1N1 strain (n=445,431)
    84.0
    15.2%
    81.2
    14.5%
    A/H3N2 strain (n=377,369)
    71.1
    12.9%
    69.5
    12.4%
    B strain (n=321,320)
    60.6
    11%
    60.3
    10.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments A/H1N1 strain: Exact 2-sided, 95 percent (%) confidence intervals was computed based on the methodology by Chan and Zhang
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Non-inferiority was to be concluded if the lower limit of the 2-sided 95% CI was greater than -0.1 or -10%
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter percent difference
    Estimated Value 2.8
    Confidence Interval (2-Sided) 95%
    -1.8 to 7.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments A/H3N2 strain: Exact 2-sided, 95 % confidence intervals was computed based on the methodology by Chan and Zhang.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Non-inferiority was to be concluded if the lower limit of the 2-sided 95% CI was greater than -0.1 or -10%
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter percent difference
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    -3.9 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments B strain: Exact 2-sided, 95 % confidence intervals was computed based on the methodology by Chan and Zhang.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Non-inferiority was to be concluded if the lower limit of the 2-sided 95% CI was greater than -0.1 or -10%
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter percent difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -5.6 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose
    Description Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose at year 0 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.
    Time Frame 1 month after 13vPnC Dose at year 0

    Outcome Measure Data

    Analysis Population Description
    Evaluable immunogenicity population:eligible participants who received vaccination as assigned;had blood drawn within pre-specified time-frames;had at least 1 valid,determinate assay result;had no major protocol violation. n=participants with valid and determinate assay results for the specified serotype at the given visit.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 531 532
    Serotype 1 (n=292, 289)
    4.05
    5.45
    Serotype 3 (n=290, 288)
    1.15
    1.46
    Serotype 4 (n=290, 288)
    2.35
    3.41
    Serotype 5 (n=293, 289)
    6.03
    7.18
    Serotype 6A (n=293, 288)
    5.78
    6.70
    Serotype 6B (n=292, 289)
    7.58
    10.09
    Serotype 7F (n=293, 289)
    8.14
    10.57
    Serotype 9V (n=293, 289)
    4.96
    6.97
    Serotype 14 (n=294, 288)
    10.77
    14.05
    Serotype 18C (n=293, 288)
    9.65
    13.49
    Serotype 19A (n=294, 289)
    16.80
    18.84
    Serotype 19F (n=291, 286)
    6.13
    7.13
    Serotype 23F (n=294, 289)
    7.17
    8.54
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 1: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.58 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 3: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.66 to 0.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 4: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.55 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 5: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.67 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.70 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6B: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.60 to 0.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 7F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.63 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 9V: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric mean ratio
    Estimated Value 0.71
    Confidence Interval (2-Sided) 95%
    0.59 to 0.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 14: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.60 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 18C: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.58 to 0.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.89
    Confidence Interval (2-Sided) 95%
    0.74 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.67 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 23F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority was to be concluded if the lower limit of the 2-sided 95% CI for the GMR was greater than 0.5 (2-fold criterion).
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.66 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Month After 13vPnC (Year 5)
    Description Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 Month After 13vPnC (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.
    Time Frame 1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5 included participants who had at least 1 valid and determinate assay result related to the proposed analysis. n=participants with valid and determinate assay results for the specified serotype at 1 month after 13vPnC (Year 5) blood draws for each treatment arm, respectively.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm on Day 1(Dose 1). Placebo matched to 13vPnC vaccine (dose 2) was administered 1 month after vaccination 1, dose 1 (13vPnC+TIV).Participants were then followed-up to 4 years (for 1 month, then 6 month and then yearly follow-up) after dose 2 of vaccination 1. Participants then received 0.5 mL dose of 13vPnC vaccine intramuscular injection into the deltoid muscle of the left arm 5 years after vaccination 1. Participants were further followed-up for 1 month and then for 6 months. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 363 363
    Serotype 1 (n=349,352 )
    178
    168
    Serotype 3(n=355, 352)
    59
    66
    Serotype 4(n=357,350)
    1618
    1491
    Serotype 5(n=350,353)
    267
    312
    Serotype 6A(n=356,350)
    4266
    3994
    Serotype 6B(n=354,351)
    3583
    3567
    Serotype 7F(n=355,352)
    1636
    1803
    Serotype 9V(n=353,347)
    1818
    1551
    Serotype 14(n=355,350)
    1110
    1107
    Serotype 18C(n=353,348)
    1800
    1738
    Serotype 19A(n=354,352)
    913
    890
    Serotype 19F(n=345,338)
    1202
    1140
    Serotype 23F(n=354,350)
    1837
    1820
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 1: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.83 to 1.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 3: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.75 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 4: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.92 to 1.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 5: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.68 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.88 to 1.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6B: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.84 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 7F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.78 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 9V: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    0.93 to 1.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 14: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.86 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 18C: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.84 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.87 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.85 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 23F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.80 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) Before 13vPnC (Year 5) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants with immunogenicity data at both Year 5 endpoints.
    Time Frame before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5.n=participants with valid and determinate assay results for the specified serotype at before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws for each treatment arm, respectively.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 726
    Serotype 1:Before 13vPnC (Year 5),(n=690)
    10
    Serotype 1: After 13vPnC (Year 5),(n=690)
    173
    Serotype 3: Before 13vPnC (Year 5),(n=699)
    8
    Serotype 3: After 13vPnC (Year 5),(n=699)
    62
    Serotype 4 : Before 13vPnC (Year 5),(n=667)
    88
    Serotype 4 : After 13vPnC (Year 5),(n=667)
    1553
    Serotype 5 : Before 13vPnC (Year 5),(n=694)
    16
    Serotype 5 :After 13vPnC (Year 5),(n=694)
    290
    Serotype 6A : Before 13vPnC (Year 5),(n=677)
    173
    Serotype 6A : After 13vPnC (Year 5),(n=677)
    4072
    Serotype 6B : Before 13vPnC (Year 5),(n=650)
    209
    Serotype 6B : After 13vPnC (Year 5),(n=650)
    3504
    Serotype 7F: Before 13vPnC (Year 5),(n=687)
    122
    Serotype 7F: After 13vPnC (Year 5),(n=687)
    1697
    Serotype 9V: Before 13vPnC (Year 5),(n=671)
    97
    Serotype 9V: After 13vPnC (Year 5),(n=671)
    1669
    Serotype 14: Before 13vPnC (Year 5),(n=678)
    289
    Serotype 14: After 13vPnC (Year 5),(n=678)
    1096
    Serotype 18C: Before 13vPnC (Year 5),(n=683)
    120
    Serotype 18C: After 13vPnC (Year 5),(n=683)
    1748
    Serotype 19A: Before 13vPnC (Year 5),(n=696)
    113
    Serotype 19A: After 13vPnC (Year 5),(n=696)
    900
    Serotype 19F: Before 13vPnC (Year 5),(n=649)
    38
    Serotype 19F: After 13vPnC (Year 5),(n=649)
    1146
    Serotype 23F: Before 13vPnC (Year 5),(n=685)
    50
    Serotype 23F: After 13vPnC (Year 5),(n=685)
    1819
    5. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold-Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 5)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before 13vPnC (Year 5) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. n=participants with valid and determinate assay results for the specified serotype from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame before 13vPnC (Year 5), 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5 included participants who had at least 1 valid and determinate assay result related to the proposed analysis.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 726
    Serotype 1 (n=690)
    18.0
    Serotype 3(n=699)
    7.4
    Serotype 4(n=667)
    17.6
    Serotype 5 (n=694)
    18.4
    Serotype 6A(n=677)
    23.6
    Serotype 6B(n=650)
    16.7
    Serotype 7F(n=687)
    13.9
    Serotype 9V(n=671)
    17.3
    Serotype 14(n=678)
    3.8
    Serotype 18C(n=683)
    14.6
    Serotype 19A(n=696)
    8.0
    Serotype 19F(n=649)
    30.4
    Serotype 23F(n=685)
    36.5
    6. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.n=participants with valid and determinate assay results for the specified serotype for both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 0 and 5 included participants who had at least 1 valid and determinate assay result related to the proposed analysis.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1:After 13vPnC (Year 0),(n=381)
    217
    Serotype 1: After 13vPnC (Year 5),(n=381)
    183
    Serotype 3: After 13vPnC (Year 0),(n=374)
    69
    Serotype 3: After 13vPnC (Year 5),(n=374)
    61
    Serotype 4 : After 13vPnC (Year 0),(n=382)
    1905
    Serotype 4 : After 13vPnC (Year 5),(n=382)
    1589
    Serotype 5 : After 13vPnC (Year 0),(n=374)
    129
    Serotype 5 :After 13vPnC (Year 5),(n=374)
    300
    Serotype 6A : After 13vPnC (Year 0),(n=390)
    2779
    Serotype 6A : After 13vPnC (Year 5),(n=390)
    4196
    Serotype 6B : After 13vPnC (Year 0),(n=380)
    3089
    Serotype 6B : After 13vPnC (Year 5),(n=380)
    3541
    Serotype 7F: After 13vPnC (Year 0),(n=372)
    2196
    Serotype 7F: After 13vPnC (Year 5),(n=372)
    1768
    Serotype 9V: After 13vPnC (Year 0),(n=387)
    1343
    Serotype 9V: After 13vPnC (Year 5),(n=387)
    1768
    Serotype 14: After 13vPnC (Year 0),(n=383)
    1169
    Serotype 14: After 13vPnC (Year 5),(n=383)
    1135
    Serotype 18C: After 13vPnC (Year 0),(n=381)
    1728
    Serotype 18C: After 13vPnC (Year 5),(n=381)
    1772
    Serotype 19A: After 13vPnC (Year 0),(n=378)
    879
    Serotype 19A: After 13vPnC (Year 5),(n=378)
    858
    Serotype 19F: After 13vPnC (Year 0),(n=369)
    472
    Serotype 19F: After 13vPnC (Year 5),(n=369)
    1139
    Serotype 23F: After 13vPnC (Year 0),(n=368)
    494
    Serotype 23F: After 13vPnC (Year 5),(n=368)
    1955
    7. Other Pre-specified Outcome
    Title Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to 1 Month After 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype from both 1 month after 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1 (n=381)
    0.8
    Serotype 3(n=374)
    0.9
    Serotype 4(n=382)
    0.8
    Serotype 5 (n=374)
    2.3
    Serotype 6A(n=390)
    1.5
    Serotype 6B(n=380)
    1.1
    Serotype 7F(n=372)
    0.8
    Serotype 9V(n=387)
    1.3
    Serotype 14(n=383)
    1.0
    Serotype 18C(n=381)
    1.0
    Serotype 19A(n=378)
    1.0
    Serotype 19F(n=369)
    2.4
    Serotype 23F(n=368)
    4.0
    8. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) Before 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMTs (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws. CI for GMTs were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.
    Time Frame before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype for both before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1:Before 13vPnC (Year 0),(n=384)
    6
    Serotype 1: After 13vPnC (Year 5),(n=384)
    171
    Serotype 3: Before 13vPnC (Year 0),(n=380)
    6
    Serotype 3: After 13vPnC (Year 5),(n=380)
    60
    Serotype 4 : Before 13vPnC (Year 0),(n=310)
    22
    Serotype 4 : After 13vPnC (Year 5),(n=310)
    1558
    Serotype 5 : Before 13vPnC (Year 0),(n=370)
    5
    Serotype 5 :After 13vPnC (Year 5),(n=370)
    284
    Serotype 6A : Before 13vPnC (Year 0),(n=356)
    18
    Serotype 6A : After 13vPnC (Year 5),(n=356)
    4072
    Serotype 6B : Before 13vPnC (Year 0),(n=333)
    53
    Serotype 6B : After 13vPnC (Year 5),(n=333)
    3341
    Serotype 7F: Before 13vPnC (Year 0),(n=330)
    10
    Serotype 7F: After 13vPnC (Year 5),(n=330)
    1818
    Serotype 9V: Before 13vPnC (Year 0),(n=352)
    28
    Serotype 9V: After 13vPnC (Year 5),(n=352)
    1725
    Serotype 14: Before 13vPnC (Year 0),(n=369)
    67
    Serotype 14: After 13vPnC (Year 5),(n=369)
    1164
    Serotype 18C: Before 13vPnC (Year 0),(n=361)
    20
    Serotype 18C: After 13vPnC (Year 5),(n=361)
    1824
    Serotype 19A: Before 13vPnC (Year 0),(n=348)
    28
    Serotype 19A: After 13vPnC (Year 5),(n=348)
    849
    Serotype 19F: Before 13vPnC (Year 0),(n=377)
    14
    Serotype 19F: After 13vPnC (Year 5),(n=377)
    1106
    Serotype 23F: Before 13vPnC (Year 0),(n=350)
    9
    Serotype 23F: After 13vPnC (Year 5),(n=350)
    1851
    9. Other Pre-specified Outcome
    Title Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before13vPnC (Year 0) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype from both before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1 (n=384)
    27.5
    Serotype 3(n=380)
    9.7
    Serotype 4(n=310)
    71.8
    Serotype 5 (n=370)
    57.0
    Serotype 6A(n=356)
    224.1
    Serotype 6B(n=333)
    63.5
    Serotype 7F(n=330)
    188.0
    Serotype 9V(n=352)
    61.0
    Serotype 14(n=369)
    17.5
    Serotype 18C(n=361)
    91.7
    Serotype 19A(n=348)
    30.7
    Serotype 19F(n=377)
    80.5
    Serotype 23F(n=350)
    216.5
    10. Other Pre-specified Outcome
    Title Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) Before and 1 Month After 13vPnC (Year 0), 1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5)
    Description Serotype-specific OPA GMTs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before, 1 month after 13vPnC (Year 0), at Years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) blood draws. CI for GMT were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. n=participants with valid and determinate assay results for the specified serotype at before, 1 month after 13vPnC (Year 0), at Years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) blood draws.
    Time Frame Before,1 month after 13vPnC (Year 0), 1, 2, 3, 4 years after initial vaccination (Year 0); before,1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    Subset of all-available immunogenicity population with data at Years 0 through 5 included participants with immunogenicity data at all-time points from Year 0 through Year 5 within the protocol specified time window.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 130
    Serotype 1: Before 13vPnC dose Year 0 (n=92)
    6
    Serotype 1: After 13vPnC dose at Year 0 (n=92)
    200
    Serotype 1: Year 1 (n=125)
    19
    Serotype 1: Year 2 (n=128)
    14
    Serotype 1: Year 3 (n=128)
    11
    Serotype 1: Year 4 (n=127)
    10
    Serotype 1: Before 13vPnC dose Year 5 (n=126)
    10
    Serotype 1: After 13vPnC dose at Year 5 (n=126)
    203
    Serotype 3: Before 13vPnC dose Year 0 (n=90)
    6
    Serotype 3: After 13vPnC dose Year 0 (n=91)
    63
    Serotype 3: Year 1 (n=129)
    14
    Serotype 3: Year 2 (n=129)
    12
    Serotype 3: Year 3 (n=129)
    9
    Serotype 3: Year 4 (n=128)
    9
    Serotype 3: Before 13vPnC dose Year 5 (n=129)
    9
    Serotype 3: After 13vPnC dose at Year 5 (n=128)
    55
    Serotype 4: Before 13vPnC dose Year 0 (n=74)
    16
    Serotype 4: After 13vPnC dose at Year 0 (n=91)
    1896
    Serotype 4: Year 1 (n=126)
    442
    Serotype 4: Year 2 (n=121)
    181
    Serotype 4: Year 3 (n=125)
    137
    Serotype 4: Year 4 (n=123)
    97
    Serotype 4: Before 13vPnC dose Year 5 (n=125)
    92
    Serotype 4: After 13vPnC dose at Year 5 (n=128)
    1574
    Serotype 5: Before 13vPnC dose Year 0 (n=89)
    5
    Serotype 5: After 13vPnC dose at Year 0 (n=93)
    145
    Serotype 5: Year 1 (n=130)
    32
    Serotype 5: Year 2 (n=128)
    20
    Serotype 5: Year 3 (n=128)
    17
    Serotype 5: Year 4 (n=128)
    14
    Serotype 5: Before 13vPnC dose Year 5 (n=129)
    13
    Serotype 5: After 13vPnC dose at Year 5 (n=128)
    273
    Serotype 6A: Before 13vPnC dose Year 0 (n=87)
    16
    Serotype 6A: After 13vPnC dose Year 0 (n=94)
    2158
    Serotype 6A: Year 1 (n=126)
    748
    Serotype 6A: Year 2 (n=129)
    405
    Serotype 6A: Year 3 (n=127)
    282
    Serotype 6A: Year 4 (n=126)
    203
    Serotype 6A: Before 13vPnC dose Year 5 (n=125)
    166
    Serotype 6A: After 13vPnC dose Year 5 (n=129)
    3777
    Serotype 6B: Before 13vPnC dose Year 0 (n=83)
    88
    Serotype 6B: After 13vPnC dose Year 0 (n=93)
    2950
    Serotype 6B: Year 1 (n=122)
    765
    Serotype 6B: Year 2 (n=121)
    505
    Serotype 6B: Year 3 (n=120)
    373
    Serotype 6B: Year 4 (n=115)
    326
    Serotype 6B: Before 13vPnC dose Year 5 (n=123)
    229
    Serotype 6B: After 13vPnC dose Year 5 (n=127)
    3804
    Serotype 7F: Before 13vPnC dose Year 0 (n=80)
    13
    Serotype 7F: After 13vPnC dose Year 0 (n=88)
    2265
    Serotype 7F: Year 1 (n=129)
    515
    Serotype 7F: Year 2 (n=128)
    279
    Serotype 7F: Year 3 (n=125)
    253
    Serotype 7F: Year 4 (n=127)
    175
    Serotype 7F: Before 13vPnC dose Year 5 (n=124)
    155
    Serotype 7F: After 13vPnC dose Year 5 (n=129)
    1932
    Serotype 9V: Before 13vPnC dose Year 0 (n=88)
    17
    Serotype 9V: After 13vPnC dose Year 0 (n=93)
    1202
    Serotype 9V: Year 1 (n=125)
    276
    Serotype 9V: Year 2 (n=127)
    136
    Serotype 9V: Year 3 (n=128)
    121
    Serotype 9V: Year 4 (n=124)
    66
    Serotype 9V: Before 13vPnC dose Year 5 (n=128)
    86
    Serotype 9V: After 13vPnC dose Year 5 (n=127)
    1572
    Serotype 14: Before 13vPnC dose Year 0 (n=87)
    74
    Serotype 14: After 13vPnC dose Year 0 (n=90)
    1436
    Serotype 14: Year 1 (n=124)
    541
    Serotype 14: Year 2 (n=125)
    446
    Serotype 14: Year 3 (n=124)
    416
    Serotype 14: Year 4 (n=125)
    341
    Serotype 14: Before 13vPnC dose Year 5 (n=127)
    335
    Serotype 14: After 13vPnC dose Year 5 (n=128)
    1238
    Serotype 18C: Before 13vPnC dose Year 0 (n=82)
    18
    Serotype 18C: After 13vPnC dose Year 0 (n=92)
    1189
    Serotype 18C: Year 1 (n=127)
    301
    Serotype 18C: Year 2 (n=123)
    170
    Serotype 18C: Year 3 (n=129)
    115
    Serotype 18C: Year 4 (n=126)
    102
    Serotype 18C: Before 13vPnC dose Year 5 (n=127)
    99
    Serotype 18C: After 13vPnC dose Year 5 (n=127)
    1580
    Serotype 19A: Before 13vPnC dose Year 0 (n=84)
    24
    Serotype 19A: After 13vPnC dose Year 0 (n=92)
    727
    Serotype 19A: Year 1 (n=130)
    193
    Serotype 19A: Year 2 (n=127)
    135
    Serotype 19A: Year 3 (n=129)
    105
    Serotype 19A: Year 4 (n=129)
    97
    Serotype 19A: Before 13vPnC dose Year 5 (n=130)
    97
    Serotype 19A: After 13vPnC dose Year 5 (n=128)
    874
    Serotype 19F: Before 13vPnC dose Year 0 (n=94)
    14
    Serotype 19F: After 13vPnC dose Year 0 (n=91)
    448
    Serotype 19F: Year 1 (n=124)
    85
    Serotype 19F: Year 2 (n=128)
    44
    Serotype 19F: Year 3 (n=128)
    35
    Serotype 19F: Year 4 (n=125)
    29
    Serotype 19F: Before 13vPnC dose Year 5 (n=125)
    24
    Serotype 19F: After 13vPnC dose Year 5 (n=125)
    1112
    Serotype 23F: Before 13vPnC dose Year 0 (n=84)
    9
    Serotype 23F: After 13vPnC dose Year 0 (n=89)
    396
    Serotype 23F: Year 1 (n=127)
    116
    Serotype 23F: Year 2 (n=124)
    95
    Serotype 23F: Year 3 (n=128)
    60
    Serotype 23F: Year 4 (n=127)
    54
    Serotype 23F: Before 13vPnC dose Year 5 (n=127)
    48
    Serotype 23F: After 13vPnC dose Year 5 (n=128)
    1642
    11. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC (Year 0),1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) Relative to Before 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before to 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both the baseline and the various time points.
    Time Frame Before, 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    Subset of all-available immunogenicity population with data at Years 0 through 5 included participants with immunogenicity data at all-time points from Year 0 through Year 5 within the protocol specified time window. n=participants with valid and determinate assay results for both the before 13vPnC (Year 0) and all the specified timepoints.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 130
    Serotype 1:After 13vPnC dose at Year 0 (n=89)
    34.0
    Serotype 1: Year 1 (n= 90)
    3.5
    Serotype 1: Year 2 (n=91)
    2.4
    Serotype 1: Year 3 (n= 92)
    1.8
    Serotype 1: Year 4 (n= 90)
    1.6
    Serotype 1: Before 13vPnC dose Year 5 (n=89)
    1.7
    Serotype 1: After 13vPnC dose at Year 5 (n=89)
    39.3
    Serotype 3: After 13vPnC dose at Year 0 (n=87)
    10.4
    Serotype 3: Year 1 (n=89)
    2.0
    Serotype 3: Year 2 (n=89)
    1.6
    Serotype 3: Year 3 (n=89)
    1.3
    Serotype 3: Year 4 (n=89)
    1.4
    Serotype 3: Before 13vPnC dose Year 5 (n=90)
    1.5
    Serotype 3: After 13vPnC dose at Year 5 (n=89)
    9.1
    Serotype 4: After 13vPnC dose at Year 0 (n=72)
    118.9
    Serotype 4: Year 1 (n=74)
    21.3
    Serotype 4: Year 2 (n=71)
    8.3
    Serotype 4: Year 3 (n=70)
    6.5
    Serotype 4: Year 4 (n=71)
    4.6
    Serotype 4: Before 13vPnC dose Year 5 (n=71)
    4.7
    Serotype 4: After 13vPnC dose at Year 5 (n=73)
    98.7
    Serotype 5: After 13vPnC dose at Year 0 (n=87)
    29.5
    Serotype 5: Year 1 (n=89)
    6.1
    Serotype 5: Year 2 (n=88)
    3.7
    Serotype 5: Year 3 (n=88)
    2.9
    Serotype 5: Year 4 (n=88)
    2.6
    Serotype 5: Before 13vPnC dose Year 5 (n=88)
    2.3
    Serotype 5: After 13vPnC dose at Year 5 (n=87)
    60.6
    Serotype 6A: After 13vPnC dose Year 0 (n=86)
    126.8
    Serotype 6A: Year 1 (n=85)
    38.3
    Serotype 6A: Year 2 (n=87)
    21.9
    Serotype 6A: Year 3 (n=86)
    14.8
    Serotype 6A: Year 4 (n=85)
    11.7
    Serotype 6A: Before 13vPnC dose Year 5 (n=85)
    9.2
    Serotype 6A: After 13vPnC dose Year 5 (n=86)
    219.2
    Serotype 6B: After 13vPnC dose Year 0 (n=81)
    33.3
    Serotype 6B: Year 1 (n=78)
    8.9
    Serotype 6B: Year 2 (n=78)
    5.7
    Serotype 6B: Year 3 (n=77)
    4.3
    Serotype 6B: Year 4 (n=73)
    3.3
    Serotype 6B: Before 13vPnC dose Year 5 (n=81)
    2.9
    Serotype 6B: After 13vPnC dose Year 5 (n=81)
    38.8
    Serotype 7F: After 13vPnC dose Year 0 (n=75)
    168.6
    Serotype 7F: Year 1 (n=80)
    37.1
    Serotype 7F: Year 2 (n=78)
    18.7
    Serotype 7F: Year 3 (n=76)
    17.8
    Serotype 7F: Year 4 (n=78)
    10.4
    Serotype 7F: Before 13vPnC dose Year 5 (n=77)
    8.4
    Serotype 7F: After 13vPnC dose Year 5 (n=80)
    163.6
    Serotype 9V: After 13vPnC dose Year 0 (n=86)
    68.2
    Serotype 9V: Year 1 (n=86)
    12.2
    Serotype 9V: Year 2 (n=87)
    5.6
    Serotype 9V: Year 3 (n=88)
    5.3
    Serotype 9V: Year 4 (n=84)
    3.0
    Serotype 9V: Before 13vPnC dose Year 5 (n=87)
    3.8
    Serotype 9V: After 13vPnC dose Year 5 (n=86)
    99.3
    Serotype 14: After 13vPnC dose Year 0 (n=83)
    22.4
    Serotype 14: Year 1 (n=84)
    7.3
    Serotype 14: Year 2 (n=85)
    6.2
    Serotype 14: Year 3 (n=82)
    5.2
    Serotype 14: Year 4 (n=84)
    5.5
    Serotype 14: Before 13vPnC dose Year 5 (n=86)
    4.7
    Serotype 14: After 13vPnC dose Year 5 (n=86)
    19.9
    Serotype 18C: After 13vPnC dose Year 0 (n=79)
    58.2
    Serotype 18C: Year 1 (n=81)
    12.3
    Serotype 18C: Year 2 (n=81)
    6.2
    Serotype 18C: Year 3 (n=81)
    4.5
    Serotype 18C: Year 4 (n=79)
    3.9
    Serotype 18C: Before 13vPnC dose Year 5 (n=81)
    3.9
    Serotype 18C: After 13vPnC dose Year 5 (n=79)
    82.7
    Serotype 19A: After 13vPnC dose Year 0 (n=81)
    28.4
    Serotype 19A: Year 1 (n=84)
    7.3
    Serotype 19A: Year 2 (n=82)
    5.4
    Serotype 19A: Year 3 (n=84)
    4.1
    Serotype 19A: Year 4 (n=84)
    3.7
    Serotype 19A: Before 13vPnC dose Year 5 (n=84)
    3.8
    Serotype 19A: After 13vPnC dose Year 5 (n=83)
    36.4
    Serotype 19F: After 13vPnC dose Year 0 (n=90)
    32.8
    Serotype 19F: Year 1 (n=91)
    6.3
    Serotype 19F: Year 2 (n=93)
    3.9
    Serotype 19F: Year 3 (n=92)
    2.7
    Serotype 19F: Year 4 (n=91)
    2.4
    Serotype 19F: Before 13vPnC dose Year 5 (n=90)
    1.9
    Serotype 19F: After 13vPnC dose Year 5 (n=89)
    81.6
    Serotype 23F: After 13vPnC dose Year 0 (n=79)
    41.2
    Serotype 23F: Year 1 (n=84)
    12.6
    Serotype 23F: Year 2 (n=81)
    9.6
    Serotype 23F: Year 3 (n=84)
    6.6
    Serotype 23F: Year 4 (n=84)
    5.8
    Serotype 23F: Before 13vPnC dose Year 5 (n=83)
    5.3
    Serotype 23F: After 13vPnC dose Year 5 (n=82)
    194.0
    12. Other Pre-specified Outcome
    Title Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) 1 Month After 13vPnC (Year 5)
    Description Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 1 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.
    Time Frame 1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5. n=participants with valid and determinate assay results for the specified serotype at 1 month after 13vPnC (Year 5) blood draws for each treatment arm, respectively.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm on Day 1(Dose 1). Placebo matched to 13vPnC vaccine (dose 2) was administered 1 month after vaccination 1, dose 1 (13vPnC+TIV).Participants were then followed-up to 4 years (for 1 month, then 6 month and then yearly follow-up) after dose 2 of vaccination 1. Participants then received 0.5 mL dose of 13vPnC vaccine intramuscular injection into the deltoid muscle of the left arm 5 years after vaccination 1. Participants were further followed-up for 1 month and then for 6 months. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 363 363
    Serotype 1 (n=357, 345)
    5.92
    5.83
    Serotype 3(n=343, 338)
    0.69
    0.72
    Serotype 4(n=357,345)
    4.90
    4.77
    Serotype 5(n=357,345)
    7.49
    8.02
    Serotype 6A(n=357,345)
    13.59
    13.45
    Serotype 6B(n=355,345)
    20.18
    21.76
    Serotype 7F(n=357,345)
    8.48
    8.70
    Serotype 9V(n=357,345)
    5.91
    6.35
    Serotype 14(n=357,345)
    15.57
    16.39
    Serotype 18C(n=357,345)
    7.77
    8.46
    Serotype 19A(n=357,345)
    16.77
    17.97
    Serotype 19F(n=357,345)
    16.83
    18.18
    Serotype 23F(n=357,345)
    18.15
    20.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 1: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.87 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 3: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.82 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 4: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    0.88 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 5: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.80 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.84 to 1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 6B: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.77 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 7F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.85 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 9V: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.81 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 14: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.81 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 18C: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    0.79 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19A: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.80 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 19F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.77 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5), Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Comments Serotype 23F: 2-sided 95 % CI for the ratio of 2 geometric means (13vPnC+TIV/Placebo and Placebo+TIV/13vPnC) was constructed by back transformation of the CIs for the difference of the 2 logarithmically transformed assay results computed using the Student t distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Geometric Mean Ratio
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.74 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) Before 13vPnC (Year 5) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both Year 5 time points.
    Time Frame before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5. n=participants with valid and determinate assay results for the specified serotype at before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 726
    Serotype 1:Before 13vPnC (Year 5),(n=665)
    1.27
    Serotype 1: After 13vPnC (Year 5),(n=665)
    5.87
    Serotype 3: Before 13vPnC (Year 5),(n=623)
    0.33
    Serotype 3: After 13vPnC (Year 5),(n=623)
    0.71
    Serotype 4 : Before 13vPnC (Year 5),(n=663)
    0.67
    Serotype 4 : After 13vPnC (Year 5),(n=663)
    4.83
    Serotype 5 : Before 13vPnC (Year 5),(n=671)
    2.65
    Serotype 5 :After 13vPnC (Year 5),(n=671)
    7.76
    Serotype 6A : Before 13vPnC (Year 5),(n=671)
    2.52
    Serotype 6A : After 13vPnC (Year 5),(n=671)
    13.51
    Serotype 6B : Before 13vPnC (Year 5),(n=668)
    3.12
    Serotype 6B : After 13vPnC (Year 5),(n=668)
    21.04
    Serotype 7F: Before 13vPnC (Year 5),(n=671)
    2.52
    Serotype 7F: After 13vPnC (Year 5),(n=671)
    8.72
    Serotype 9V: Before 13vPnC (Year 5),(n=672)
    2.11
    Serotype 9V: After 13vPnC (Year 5),(n=672)
    6.14
    Serotype 14: Before 13vPnC (Year 5),(n=672)
    5.17
    Serotype 14: After 13vPnC (Year 5),(n=672)
    16.26
    Serotype 18C: Before 13vPnC (Year 5),(n=672)
    2.55
    Serotype 18C: After 13vPnC (Year 5),(n=672)
    8.10
    Serotype 19A: Before 13vPnC (Year 5),(n=671)
    5.47
    Serotype 19A: After 13vPnC (Year 5),(n=671)
    17.29
    Serotype 19F: Before 13vPnC (Year 5),(n=664)
    2.24
    Serotype 19F: After 13vPnC (Year 5),(n=664)
    17.73
    Serotype 23F: Before 13vPnC (Year 5),(n=671)
    2.50
    Serotype 23F: After 13vPnC (Year 5),(n=671)
    19.23
    14. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 5)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before 13vPnC (Year 5) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame before 13vPnC (Year 5), 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Year 5. n=participants with valid and determinate assay results for the specified serotype for both before 13vPnC (Year 5) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 726
    Serotype 1 (n=665)
    4.62
    Serotype 3(n=623)
    2.11
    Serotype 4(n=663)
    7.24
    Serotype 5 (n=671)
    2.93
    Serotype 6A(n=671)
    5.35
    Serotype 6B(n=668)
    6.74
    Serotype 7F(n=671)
    3.46
    Serotype 9V(n=672)
    2.90
    Serotype 14(n=672)
    3.14
    Serotype 18C(n=672)
    3.18
    Serotype 19A(n=671)
    3.16
    Serotype 19F(n=664)
    7.93
    Serotype 23F(n=671)
    7.69
    15. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) 1 Month After 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points
    Time Frame 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype for both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1:After 13vPnC (Year 0),(n=389)
    4.77
    Serotype 1: After 13vPnC (Year 5),(n=389)
    5.88
    Serotype 3: After 13vPnC (Year 0),(n=378)
    1.26
    Serotype 3: After 13vPnC (Year 5),(n=378)
    0.74
    Serotype 4 : After 13vPnC (Year 0),(n=387)
    2.90
    Serotype 4 : After 13vPnC (Year 5),(n=387)
    5.13
    Serotype 5 : After 13vPnC (Year 0),(n=390)
    6.52
    Serotype 5 :After 13vPnC (Year 5),(n=390)
    8.25
    Serotype 6A : After 13vPnC (Year 0),(n=390)
    6.13
    Serotype 6A : After 13vPnC (Year 5),(n=390)
    13.52
    Serotype 6B : After 13vPnC (Year 0),(n=390)
    8.87
    Serotype 6B : After 13vPnC (Year 5),(n=390)
    20.70
    Serotype 7F: After 13vPnC (Year 0),(n=390)
    9.24
    Serotype 7F: After 13vPnC (Year 5),(n=390)
    8.40
    Serotype 9V: After 13vPnC (Year 0),(n=391)
    5.83
    Serotype 9V: After 13vPnC (Year 5),(n=391)
    6.07
    Serotype 14: After 13vPnC (Year 0),(n=391)
    11.98
    Serotype 14: After 13vPnC (Year 5),(n=391)
    15.04
    Serotype 18C: After 13vPnC (Year 0),(n=390)
    11.64
    Serotype 18C: After 13vPnC (Year 5),(n=390)
    8.25
    Serotype 19A: After 13vPnC (Year 0),(n=391)
    17.43
    Serotype 19A: After 13vPnC (Year 5),(n=391)
    18.48
    Serotype 19F: After 13vPnC (Year 0),(n=388)
    6.56
    Serotype 19F: After 13vPnC (Year 5),(n=388)
    18.26
    Serotype 23F: After 13vPnC (Year 0),(n=391)
    8.03
    Serotype 23F: After 13vPnC (Year 5),(n=391)
    20.17
    16. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to 1 Month After 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype for both 1 month after 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1 (n=389)
    1.23
    Serotype 3(n=378)
    0.59
    Serotype 4(n=387)
    1.77
    Serotype 5 (n=390)
    1.26
    Serotype 6A(n=390)
    2.21
    Serotype 6B(n=390)
    2.33
    Serotype 7F(n=390)
    0.91
    Serotype 9V(n=391)
    1.04
    Serotype 14(n=391)
    1.25
    Serotype 18C(n=390)
    0.71
    Serotype 19A(n=391)
    1.06
    Serotype 19F(n=388)
    2.78
    Serotype 23F(n=391)
    2.51
    17. Other Pre-specified Outcome
    Title Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMCs) Before 13vPnC (Year 0) and 1 Month After 13vPnC Re-vaccinated Dose (Year 5)
    Description Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for adult participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Participants in this population must have immunogenicity data at both the Year 0 and Year 5 time points.
    Time Frame before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype for both before 13vPnC (Year 0) and 1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1:Before 13vPnC (Year 0),(n=380)
    0.44
    Serotype 1: After 13vPnC (Year 5),(n=380)
    5.86
    Serotype 3: Before 13vPnC (Year 0),(n=368)
    0.47
    Serotype 3: After 13vPnC (Year 5),(n=368)
    0.74
    Serotype 4 : Before 13vPnC (Year 0),(n=373)
    0.22
    Serotype 4 : After 13vPnC (Year 5),(n=373)
    5.21
    Serotype 5 : Before 13vPnC (Year 0),(n=387)
    1.79
    Serotype 5 :After 13vPnC (Year 5),(n=387)
    8.32
    Serotype 6A : Before 13vPnC (Year 0),(n=386)
    1.56
    Serotype 6A : After 13vPnC (Year 5),(n=386)
    13.63
    Serotype 6B : Before 13vPnC (Year 0),(n=383)
    1.76
    Serotype 6B : After 13vPnC (Year 5),(n=383)
    21.09
    Serotype 7F: Before 13vPnC (Year 0),(n=384)
    0.70
    Serotype 7F: After 13vPnC (Year 5),(n=384)
    8.41
    Serotype 9V: Before 13vPnC (Year 0),(n=387)
    0.87
    Serotype 9V: After 13vPnC (Year 5),(n=387)
    6.07
    Serotype 14: Before 13vPnC (Year 0),(n=389)
    1.95
    Serotype 14: After 13vPnC (Year 5),(n=389)
    14.98
    Serotype 18C: Before 13vPnC (Year 0),(n=388)
    0.82
    Serotype 18C: After 13vPnC (Year 5),(n=388)
    8.24
    Serotype 19A: Before 13vPnC (Year 0),(n=388)
    2.92
    Serotype 19A: After 13vPnC (Year 5),(n=388)
    18.52
    Serotype 19F: Before 13vPnC (Year 0),(n=371)
    1.17
    Serotype 19F: After 13vPnC (Year 5),(n=371)
    18.68
    Serotype 23F: Before 13vPnC (Year 0),(n=382)
    0.97
    Serotype 23F: After 13vPnC (Year 5),(n=382)
    20.53
    18. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC Re-vaccinated Dose (Year 5) Relative to Before 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from Before 13vPnC (Year 0) to 1 month after 13vPnC re-vaccinated dose (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Time Frame Before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5)

    Outcome Measure Data

    Analysis Population Description
    All-available immunogenicity population at Years 0 and 5. n=participants with valid and determinate assay results for the specified serotype for both before 13vPnC (Year 0),1 month after 13vPnC re-vaccinated dose (Year 5) blood draws.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 598
    Serotype 1 (n=380)
    13.37
    Serotype 3(n=368)
    1.57
    Serotype 4(n=373)
    23.59
    Serotype 5 (n=387)
    4.64
    Serotype 6A(n=386)
    8.74
    Serotype 6B(n=383)
    11.96
    Serotype 7F(n=384)
    11.96
    Serotype 9V(n=387)
    6.97
    Serotype 14(n=389)
    7.68
    Serotype 18C(n=388)
    10.04
    Serotype 19A(n=388)
    6.33
    Serotype 19F(n=371)
    15.95
    Serotype 23F(n=382)
    21.18
    19. Other Pre-specified Outcome
    Title Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Before and 1 Month After 13vPnC (Year 0), 1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5)
    Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1(Dose1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1(Dose 1, placebo+TIV). Placebo matched to 13vPnC was administered 1 month after(Dose 2, placebo), or 13vPnC was administered 1 month after (Dose 2, 13vPnC).Participants were further followed-up for 1 month,then attended a 6-month follow-up visit for safety.Participants were then followed-up yearly for 4 years.Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination.Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Time Frame Before,1 month after 13vPnC (Year 0), 1, 2, 3, 4 years after initial vaccination (Year 0); before,1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    Subset of all-available immunogenicity population with data at Years 0 through 5 included participants with immunogenicity data at all-time points from Years 0 through Year 5 within the protocol specified time window. Here, n=number of participants with valid and determinate assay results for the specified serotype at the given time points.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 130
    Serotype 1: Before 13vPnC dose Year 0 (n=79)
    0.37
    Serotype 1: After 13vPnC dose at Year 0 (n=83)
    4.53
    Serotype 1: Year 1 (n=119)
    1.96
    Serotype 1: Year 2 (n=124)
    1.56
    Serotype 1: Year 3 (n=126)
    1.34
    Serotype 1: Year 4 (n=125)
    1.32
    Serotype 1: Before 13vPnC dose Year 5 (n=125)
    1.18
    Serotype 1: After 13vPnC dose at Year 5 (n=125)
    6.08
    Serotype 3: Before 13vPnC dose Year 0 (n=81)
    0.42
    Serotype 3: After 13vPnC dose Year 0 (n=82)
    1.15
    Serotype 3: Year 1 (n=115)
    0.37
    Serotype 3: Year 2 (n=122)
    0.34
    Serotype 3: Year 3 (n=119)
    0.30
    Serotype 3: Year 4 (n=117)
    0.31
    Serotype 3: Before 13vPnC dose Year 5 (n=117)
    0.30
    Serotype 3: After 13vPnC dose at Year 5 (n=121)
    0.66
    Serotype 4: Before 13vPnC dose Year 0 (n=80)
    0.19
    Serotype 4: After 13vPnC dose at Year 0 (n=82)
    2.41
    Serotype 4: Year 1 (n=118)
    0.98
    Serotype 4: Year 2 (n=123)
    0.77
    Serotype 4: Year 3 (n=125)
    0.67
    Serotype 4: Year 4 (n=125)
    0.64
    Serotype 4: Before 13vPnC dose Year 5 (n=122)
    0.58
    Serotype 4: After 13vPnC dose at Year 5 (n=125)
    4.62
    Serotype 5: Before 13vPnC dose Year 0 (n=82)
    1.40
    Serotype 5: After 13vPnC dose at Year 0 (n=83)
    5.80
    Serotype 5: Year 1 (n=118)
    3.10
    Serotype 5: Year 2 (n=124)
    2.62
    Serotype 5: Year 3 (n=126)
    2.40
    Serotype 5: Year 4 (n=125)
    2.44
    Serotype 5: Before 13vPnC dose Year 5 (n=125)
    2.41
    Serotype 5: After 13vPnC dose at Year 5 (n=125)
    7.14
    Serotype 6A: Before 13vPnC dose Year 0 (n=82)
    1.34
    Serotype 6A: After 13vPnC dose Year 0 (n=83)
    5.74
    Serotype 6A: Year 1 (n=119)
    3.64
    Serotype 6A: Year 2 (n=124)
    3.10
    Serotype 6A: Year 3 (n=126)
    2.76
    Serotype 6A: Year 4 (n=126)
    2.74
    Serotype 6A: Before 13vPnC dose Year 5 (n=125)
    2.63
    Serotype 6A: After 13vPnC dose Year 5 (n=125)
    14.31
    Serotype 6B: Before 13vPnC dose Year 0 (n=81)
    1.56
    Serotype 6B: After 13vPnC dose Year 0 (n=83)
    8.24
    Serotype 6B: Year 1 (n=119)
    4.96
    Serotype 6B: Year 2 (n=124)
    3.97
    Serotype 6B: Year 3 (n=126)
    3.58
    Serotype 6B: Year 4 (n=126)
    3.53
    Serotype 6B: Before 13vPnC dose Year 5 (n=125)
    3.18
    Serotype 6B: After 13vPnC dose Year 5 (n=124)
    21.61
    Serotype 7F: Before 13vPnC dose Year 0 (n=81)
    0.64
    Serotype 7F: After 13vPnC dose Year 0 (n=83)
    9.14
    Serotype 7F: Year 1 (n=119)
    3.82
    Serotype 7F: Year 2 (n=124)
    3.10
    Serotype 7F: Year 3 (n=126)
    2.58
    Serotype 7F: Year 4 (n=126)
    2.55
    Serotype 7F: Before 13vPnC dose Year 5 (n=124)
    2.36
    Serotype 7F: After 13vPnC dose Year 5 (n=125)
    8.05
    Serotype 9V: Before 13vPnC dose Year 0 (n=80)
    0.77
    Serotype 9V: After 13vPnC dose Year 0 (n=83)
    4.58
    Serotype 9V: Year 1 (n=119)
    2.84
    Serotype 9V: Year 2 (n=124)
    2.37
    Serotype 9V: Year 3 (n=126)
    2.16
    Serotype 9V: Year 4 (n=126)
    2.09
    Serotype 9V: Before 13vPnC dose Year 5 (n=125)
    1.97
    Serotype 9V: After 13vPnC dose Year 5 (n=125)
    5.99
    Serotype 14: Before 13vPnC dose Year 0 (n=82)
    2.21
    Serotype 14: After 13vPnC dose Year 0 (n=83)
    14.48
    Serotype 14: Year 1 (n=119)
    7.71
    Serotype 14: Year 2 (n=124)
    6.82
    Serotype 14: Year 3 (n=126)
    5.71
    Serotype 14: Year 4 (n=126)
    5.31
    Serotype 14: Before 13vPnC dose Year 5 (n=125)
    5.30
    Serotype 14: After 13vPnC dose Year 5 (n=125)
    16.85
    Serotype 18C: Before 13vPnC dose Year 0 (n=82)
    0.81
    Serotype 18C: After 13vPnC dose Year 0 (n=83)
    8.11
    Serotype 18C: Year 1 (n=119)
    3.45
    Serotype 18C: Year 2 (n=124)
    2.82
    Serotype 18C: Year 3 (n=126)
    2.38
    Serotype 18C: Year 4 (n=126)
    2.44
    Serotype 18C: Before 13vPnC dose Year 5 (n=125)
    2.26
    Serotype 18C: After 13vPnC dose Year 5 (n=125)
    6.94
    Serotype 19A: Before 13vPnC dose Year 0 (n=82)
    2.57
    Serotype 19A: After 13vPnC dose Year 0 (n=83)
    14.11
    Serotype 19A: Year 1 (n=119)
    6.95
    Serotype 19A: Year 2 (n=124)
    6.13
    Serotype 19A: Year 3 (n=126)
    5.60
    Serotype 19A: Year 4 (n=126)
    5.47
    Serotype 19A: Before 13vPnC dose Year 5 (n=125)
    5.11
    Serotype 19A: After 13vPnC dose Year 5 (n=125)
    15.77
    Serotype 19F: Before 13vPnC dose Year 0 (n=78)
    0.99
    Serotype 19F: After 13vPnC dose Year 0 (n=83)
    5.64
    Serotype 19F: Year 1 (n=118)
    2.87
    Serotype 19F: Year 2 (n=121)
    2.55
    Serotype 19F: Year 3 (n=124)
    2.28
    Serotype 19F: Year 4 (n=125)
    2.26
    Serotype 19F: Before 13vPnC dose Year 5 (n=123)
    2.10
    Serotype 19F: After 13vPnC dose Year 5 (n=125)
    17.37
    Serotype 23F: Before 13vPnC dose Year 0 (n=80)
    0.97
    Serotype 23F: After 13vPnC dose Year 0 (n=83)
    6.06
    Serotype 23F: Year 1 (n=118)
    3.65
    Serotype 23F: Year 2 (n=123)
    2.93
    Serotype 23F: Year 3 (n=126)
    2.67
    Serotype 23F: Year 4 (n=126)
    2.62
    Serotype 23F: Before 13vPnC dose Year 5 (n=125)
    2.50
    Serotype 23F: After 13vPnC dose Year 5 (n=125)
    16.95
    20. Other Pre-specified Outcome
    Title Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Fold Rises (GMFRs) 1 Month After 13vPnC (Year 0),1, 2, 3, 4 Years After Initial Vaccination (Year 0); Before and 1 Month After 13vPnC (Year 5) Relative to Before 13vPnC (Year 0)
    Description GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined from before to 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5) and were summarized geometric means and 2-sided 95% CIs, which were computed using the logarithmically transformed assay results. CI for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rises. GMFRs were calculated using all participants with available data from both the baseline and the various time points.
    Time Frame Before, 1 month after 13vPnC (Year 0), at years 1, 2, 3 and 4 after initial vaccination (Year 0), before, 1 month after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    Subset of all-available immunogenicity population with data at Years 0 through 5 included participants with immunogenicity data at all-time points from Year 0 through Year 5 within the protocol specified time window. n=participants with valid and determinate assay results for both the before 13vPnC (Year 0) and the specified timepoints.
    Arm/Group Title All Participants
    Arm/Group Description Participants received either 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV), or placebo matched to 13vPnC intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL TIV intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). One month after, participants received either Placebo matched to 13vPnC (Dose 2, placebo), or 13vPnC (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 130
    Serotype 1:After 13vPnC dose at Year 0 (n=79)
    12.50
    Serotype 1: Year 1 (n=72)
    5.64
    Serotype 1: Year 2 (n=75)
    4.73
    Serotype 1: Year 3 (n=76)
    4.01
    Serotype 1: Year 4 (n=75)
    3.79
    Serotype 1: Before 13vPnC dose Year 5 (n=76)
    3.41
    Serotype 1: After 13vPnC dose at Year 5 (n=77)
    15.25
    Serotype 3: After 13vPnC dose at Year 0 (n=80)
    2.69
    Serotype 3: Year 1 (n=73)
    0.89
    Serotype 3: Year 2 (n=77)
    0.77
    Serotype 3: Year 3 (n= 77)
    0.72
    Serotype 3: Year 4 (n=72)
    0.69
    Serotype 3: Before 13vPnC dose Year 5 (n=74)
    0.65
    Serotype 3: After 13vPnC dose at Year 5 (n=78)
    1.51
    Serotype 4: After 13vPnC dose at Year 0 (n=79)
    12.81
    Serotype 4: Year 1 (n=74)
    6.00
    Serotype 4: Year 2 (n=75)
    4.63
    Serotype 4: Year 3 (n=77)
    4.12
    Serotype 4: Year 4 (n=76)
    3.82
    Serotype 4: Before 13vPnC dose Year 5 (n=77)
    3.41
    Serotype 4: After 13vPnC dose at Year 5 (n=78)
    24.99
    Serotype 5: After 13vPnC dose at Year 0 (n=82)
    4.21
    Serotype 5: Year 1 (n=75)
    2.43
    Serotype 5: Year 2 (n=78)
    2.05
    Serotype 5: Year 3 (n=79)
    1.86
    Serotype 5: Year 4 (n=78)
    1.84
    Serotype 5: Before 13vPnC dose Year 5 (n=79)
    1.74
    Serotype 5: After 13vPnC dose at Year 5 (n=80)
    5.38
    Serotype 6A: After 13vPnC dose Year 0 (n=82)
    4.32
    Serotype 6A: Year 1 (n=75)
    2.66
    Serotype 6A: Year 2 (n=78)
    2.15
    Serotype 6A: Year 3 (n=79)
    1.96
    Serotype 6A: Year 4 (n=78)
    1.91
    Serotype 6A: Before 13vPnC dose Year 5 (n=79)
    1.74
    Serotype 6A: After 13vPnC dose Year 5 (n=80)
    10.18
    Serotype 6B: After 13vPnC dose Year 0 (n=81)
    5.50
    Serotype 6B: Year 1 (n=74)
    3.24
    Serotype 6B: Year 2 (n=77)
    2.59
    Serotype 6B: Year 3 (n=78)
    2.36
    Serotype 6B: Year 4 (n=77)
    2.20
    Serotype 6B: Before 13vPnC dose Year 5 (n=78)
    1.92
    Serotype 6B: After 13vPnC dose Year 5 (n=79)
    12.82
    Serotype 7F: After 13vPnC dose Year 0 (n=81)
    14.60
    Serotype 7F: Year 1 (n=75)
    6.28
    Serotype 7F: Year 2 (n=77)
    5.03
    Serotype 7F: Year 3 (n=78)
    4.12
    Serotype 7F: Year 4 (n=77)
    3.87
    Serotype 7F: Before 13vPnC dose Year 5 (n=77)
    3.63
    Serotype 7F: After 13vPnC dose Year 5 (n=79)
    11.65
    Serotype 9V: After 13vPnC dose Year 0 (n=80)
    5.81
    Serotype 9V: Year 1 (n=75)
    3.34
    Serotype 9V: Year 2 (n=77)
    2.90
    Serotype 9V: Year 3 (n=77)
    2.60
    Serotype 9V: Year 4 (n=76)
    2.51
    Serotype 9V: Before 13vPnC dose Year 5 (n=77)
    2.24
    Serotype 9V: After 13vPnC dose Year 5 (n=78)
    7.35
    Serotype 14: After 13vPnC dose Year 0 (n=82)
    6.47
    Serotype 14: Year 1 (n=75)
    4.00
    Serotype 14: Year 2 (n=78)
    3.54
    Serotype 14: Year 3 (n=79)
    3.10
    Serotype 14: Year 4 (n=78)
    2.84
    Serotype 14: Before 13vPnC dose Year 5 (n=79)
    2.68
    Serotype 14: After 13vPnC dose Year 5 (n=80)
    6.94
    Serotype 18C: After 13vPnC dose Year 0 (n=82)
    9.86
    Serotype 18C: Year 1 (n=75)
    4.56
    Serotype 18C: Year 2 (n=78)
    3.74
    Serotype 18C: Year 3 (n=79)
    3.11
    Serotype 18C: Year 4 (n=78)
    2.97
    Serotype 18C: Before 13vPnC dose Year 5 (n=79)
    2.77
    Serotype 18C: After 13vPnC dose Year 5 (n=80)
    8.73
    Serotype 19A: After 13vPnC dose Year 0 (n=82)
    5.52
    Serotype 19A: Year 1 (n=75)
    2.69
    Serotype 19A: Year 2 (n=78)
    2.39
    Serotype 19A: Year 3 (n=79)
    2.14
    Serotype 19A: Year 4 (n=78)
    2.06
    Serotype 19A: Before 13vPnC dose Year 5 (n=79)
    1.87
    Serotype 19A: After 13vPnC dose Year 5 (n=80)
    6.00
    Serotype 19F: After 13vPnC dose Year 0 (n=78)
    6.02
    Serotype 19F: Year 1 (n=71)
    3.39
    Serotype 19F: Year 2 (n=72)
    2.74
    Serotype 19F: Year 3 (n=76)
    2.42
    Serotype 19F: Year 4 (n=75)
    2.24
    Serotype 19F: Before 13vPnC dose Year 5 (n=74)
    2.01
    Serotype 19F: After 13vPnC dose Year 5 (n=76)
    18.16
    Serotype 23F: After 13vPnC dose Year 0 (n=80)
    6.65
    Serotype 23F: Year 1 (n=73)
    3.57
    Serotype 23F: Year 2 (n=75)
    3.09
    Serotype 23F: Year 3 (n=77)
    2.93
    Serotype 23F: Year 4 (n=76)
    2.77
    Serotype 23F: Before 13vPnC dose Year 5 (n=77)
    2.48
    Serotype 23F: After 13vPnC dose Year 5 (n=78)
    16.52
    21. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After Dose 1 (Year 0)
    Description Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder). Local reactions were measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.
    Time Frame Within 14 days after Dose 1 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    Redness: Any (n=282,263)
    16.3
    3%
    3.0
    0.5%
    Redness: Mild (n=281,262)
    15.7
    2.8%
    2.7
    0.5%
    Redness: Moderate (n=265,258)
    4.2
    0.8%
    0.4
    0.1%
    Redness: Severe (n=262,257)
    0.4
    0.1%
    0.0
    0%
    Swelling: Any (n=288,263)
    18.4
    3.3%
    3.0
    0.5%
    Swelling: Mild (n=288,263)
    17.0
    3.1%
    3.0
    0.5%
    Swelling: Moderate (n=263,257)
    5.7
    1%
    0.0
    0%
    Swelling: Severe (262,257)
    0.4
    0.1%
    0.0
    0%
    Pain: Any (n=469,321)
    86.8
    15.8%
    37.1
    6.6%
    Pain: Mild (n=459, 318)
    82.8
    15%
    35.2
    6.3%
    Pain: Moderate (n=324,261)
    39.2
    7.1%
    4.2
    0.8%
    Pain: Severe (n=267,258)
    4.1
    0.7%
    0.4
    0.1%
    Limitation of arm movement:Any(317,270)
    35.6
    6.5%
    8.9
    1.6%
    Limitation of arm movement:Mild(n=310,268)
    32.6
    5.9%
    8.2
    1.5%
    Limitation of arm movement: Moderate(n=269,259)
    5.2
    0.9%
    1.2
    0.2%
    Limitation of arm movement:Severe(n=266,258)
    3.4
    0.6%
    0.8
    0.1%
    22. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After Dose 2 (Year 0)
    Description Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder). Local reactions were measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.
    Time Frame Within 14 days after Dose 2 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data. Here,n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    Redness: Any (n=238,257)
    1.7
    0.3%
    12.1
    2.2%
    Redness: Mild (n=238,255)
    1.7
    0.3%
    10.2
    1.8%
    Redness: Moderate (n=236,248)
    0.0
    0%
    5.6
    1%
    Redness: Severe (n=236,242)
    0.0
    0%
    1.2
    0.2%
    Swelling: Any (n=242,265)
    4.5
    0.8%
    14.7
    2.6%
    Swelling: Mild (n=242,260)
    4.5
    0.8%
    12.3
    2.2%
    Swelling: Moderate (n=236,249)
    0.4
    0.1%
    6.4
    1.1%
    Swelling: Severe (236,241)
    0.0
    0%
    0.4
    0.1%
    Pain: Any (n=294,453)
    32.0
    5.8%
    84.5
    15.1%
    Pain: Mild (n=290, 431)
    30.7
    5.6%
    82.1
    14.7%
    Pain: Moderate (n=243,319)
    4.5
    0.8%
    41.1
    7.3%
    Pain: Severe (n=236,248)
    0.0
    0%
    4.8
    0.9%
    Limitation of arm movement:Any(248,318)
    9.3
    1.7%
    42.5
    7.6%
    Limitation of arm movement:Mild(n=248,316)
    9.3
    1.7%
    41.1
    7.3%
    Limitation of arm movement: Moderate(n=236,248)
    0.4
    0.1%
    5.2
    0.9%
    Limitation of arm movement:Severe(n=236,244)
    0.0
    0%
    2.9
    0.5%
    23. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Local Reactions Within 14 Days After 13vPnC (Year 5)
    Description Specific local reactions were prompted for each day,and reported using an electronic diary.Redness and Swelling were scaled as Any(redness present or swelling present);Mild(2.5 to 5.0 centimeters [cm]);Moderate(5.1 to 10.0 cm);Severe (>10 cm). Pain at injection site was scaled as: Any (pain present); Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating, with inability to do usual activity). Limitation of arm movement was scaled as Any(no limitation of arm movement);Mild(some limitation of arm movement);Moderate (unable to move arm above head but able to move arm above shoulder);Severe (unable to move arm above shoulder).
    Time Frame Within 14 days after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    The safety population at Year 5 included participants who received both (Year 0 and Year 5) 13vPnC and had some safety results at Year 5. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 364 363
    Redness: Any (n=216,215)
    15.7
    2.8%
    20.9
    3.7%
    Redness: Mild (n=215,212)
    14.0
    2.5%
    17.5
    3.1%
    Redness: Moderate (n=210,211)
    7.1
    1.3%
    12.3
    2.2%
    Redness: Severe (n=205,202)
    1.5
    0.3%
    0.5
    0.1%
    Swelling: Any (n=224,216)
    18.8
    3.4%
    18.1
    3.2%
    Swelling: Mild (n=223,214)
    17.5
    3.2%
    15.9
    2.8%
    Swelling: Moderate (n=211,208)
    7.1
    1.3%
    9.6
    1.7%
    Swelling: Severe (205,203)
    0.0
    0%
    1.0
    0.2%
    Pain: Any (n=313,306)
    79.2
    14.4%
    79.4
    14.2%
    Pain: Mild (n=297, 299)
    76.4
    13.9%
    74.9
    13.4%
    Pain: Moderate (n=248,235)
    32.7
    5.9%
    34.9
    6.2%
    Pain: Severe (n=206,205)
    4.4
    0.8%
    3.4
    0.6%
    Limitation of arm movement:Any(233,224)
    23.2
    4.2%
    26.3
    4.7%
    Limitation of arm movement:Mild(n=233,219)
    22.3
    4%
    22.8
    4.1%
    Limitation of arm movement: Moderate(n=208,206)
    2.9
    0.5%
    3.9
    0.7%
    Limitation of arm movement:Severe(n=206,206)
    1.9
    0.3%
    3.4
    0.6%
    24. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After Dose 1 (Year 0)
    Description Percentage of participants who experienced specific systemic events (mild: 38.0 to 38.4 degrees Celsius [C], moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening greater than [>] 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.
    Time Frame Within 14 days after Dose 1 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    Fever: >=38 but <38.5 degree C(n=261,259)
    1.5
    0.3%
    1.2
    0.2%
    Fever: >=38.5 but <39 degree C(n=262,257)
    1.5
    0.3%
    0.0
    0%
    Fever: >=39 but =<40.0 degree C(n=261,257)
    0.4
    0.1%
    0.0
    0%
    Fever:>40.0 degree C (n=261,257)
    0.0
    0%
    0.4
    0.1%
    Fatigue(n=389,359)
    58.1
    10.5%
    52.4
    9.4%
    Headache(n=399,382)
    65.9
    12%
    56.5
    10.1%
    Chills(n=306,291)
    31.4
    5.7%
    21.0
    3.8%
    Rash(n=278,264)
    12.6
    2.3%
    4.9
    0.9%
    Vomiting(n=266,262)
    5.3
    1%
    3.4
    0.6%
    Decreased appetite(n=315,301)
    30.2
    5.5%
    22.6
    4%
    New generalized muscle pain(n=385,326)
    65.5
    11.9%
    37.7
    6.7%
    Aggravated generalized muscle pain(n=314,294)
    34.7
    6.3%
    24.1
    4.3%
    New generalized joint pain(n=309,296)
    33.0
    6%
    24.7
    4.4%
    Aggravated generalized joint pain(n=292,284)
    21.2
    3.8%
    18.0
    3.2%
    25. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After Dose 2 (Year 0)
    Description Percentage of participants who experienced specific systemic events (absent: 38.0 degrees Celsius [C], mild: 38.0 to 38.4 degrees C, moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening > 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.
    Time Frame Within 14 days after Dose 2 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    Fever: >=38 but <38.5 degree C(n=238,241)
    1.3
    0.2%
    1.2
    0.2%
    Fever: >=38.5 but <39 degree C(n=239,240)
    1.3
    0.2%
    0.8
    0.1%
    Fever: >=39 but =<40 degree (n=236,240)
    0.4
    0.1%
    0.4
    0.1%
    Fever: >40.0 degree C(n=237,240)
    0.4
    0.1%
    0.0
    0%
    Fatigue (n=316,338)
    43.7
    7.9%
    51.8
    9.3%
    Headache (n=334,338)
    48.2
    8.7%
    50.9
    9.1%
    Chills (n=273,276)
    20.5
    3.7%
    24.6
    4.4%
    Rash (n=246,252)
    6.1
    1.1%
    9.5
    1.7%
    Vomiting (n=247,247)
    6.9
    1.3%
    6.1
    1.1%
    Decreased appetite(n=270,279)
    20.4
    3.7%
    25.8
    4.6%
    New generalized muscle pain(n=288,350)
    28.5
    5.2%
    59.1
    10.6%
    Aggravated generalized muscle pain(n=268,305)
    18.7
    3.4%
    36.7
    6.6%
    New generalized joint pain(n=268,285)
    20.5
    3.7%
    27.4
    4.9%
    Aggravated generalized joint pain(n=264,282)
    15.5
    2.8%
    23.8
    4.3%
    26. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Systemic Events Within 14 Days After 13vPnC (Year 5)
    Description Percentage of participants who experienced specific systemic events (Fever: >= 38.0 degrees Celsius [C], mild: 38.0 to 38.4 degrees C, moderate: 38.5 to 38.9 degrees C, severe: 39.0 to 40.0 degrees C and potentially life threatening > 40.0 degrees C), chills, fatigue, headache, vomiting, decreased appetite, rash, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain, and aggravated generalized joint pain prompted for each day were reported using an electronic diary.
    Time Frame Within 14 days after 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    The safety population at Year 5 included participants who received both (Year 0 and Year 5) 13vPnC and had some safety results at Year 5. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 364 363
    Fever: >= 38.0 degrees C (n=206,209)
    2.4
    0.4%
    5.3
    0.9%
    Fever: >=38 but <38.5 degree C(n=205,206)
    1.0
    0.2%
    2.4
    0.4%
    Fever: >=38.5 but <39 degree C(n=206,204)
    0.5
    0.1%
    2.0
    0.4%
    Fever: >=39 but =<40 degree C(n=205,202)
    0.0
    0%
    0.0
    0%
    Fever: >40 degree C(n=205,204)
    1.0
    0.2%
    1.5
    0.3%
    Fatigue(n=263,251)
    43.7
    7.9%
    45.8
    8.2%
    Headache(n=256,248)
    46.9
    8.5%
    51.2
    9.1%
    Chills(n=229,217)
    23.1
    4.2%
    22.1
    3.9%
    Rash(n=209,210)
    7.7
    1.4%
    13.8
    2.5%
    Vomiting(n=206,207)
    3.4
    0.6%
    7.2
    1.3%
    Decreased appetite(n=226,227)
    20.4
    3.7%
    22.0
    3.9%
    New generalized muscle pain(n=266,253)
    47.7
    8.7%
    51.0
    9.1%
    Aggravated generalized muscle pain(n=241,223)
    29.9
    5.4%
    27.4
    4.9%
    New generalized joint pain(n=219,219)
    19.2
    3.5%
    21.9
    3.9%
    Aggravated generalized joint pain(n=218,214)
    17.4
    3.2%
    18.2
    3.3%
    27. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After Dose 1 (Year 0)
    Description Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity). Acute pain was measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.
    Time Frame Within 30 Minutes After Dose 1 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    Acute pain (Dose 1):Mild
    6.7
    1.2%
    6.3
    1.1%
    Acute pain (Dose 1):Moderate
    0.0
    0%
    0.0
    0%
    Acute pain (Dose 1):Severe
    0.0
    0%
    0.0
    0%
    Acute pain (Dose 1): Any
    6.7
    1.2%
    6.3
    1.1%
    28. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After Dose 2 (Year 0)
    Description Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity). Acute pain was measured only on the participant's arm vaccinated with either 13vPnC or placebo and were not collected at the TIV injection site.
    Time Frame Within 30 Minutes After Dose 2 (Year 0)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination (Dose 2, year 0) and did not lack any safety data.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 538 543
    Acute pain (Dose 2):Mild
    5.9
    1.1%
    6.4
    1.1%
    Acute pain (Dose 2):Moderate
    0.0
    0%
    0.0
    0%
    Acute pain (Dose 2):Severe
    0.0
    0%
    0.0
    0%
    Acute pain (Dose 2):Any
    5.9
    1.1%
    6.4
    1.1%
    29. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Pre-specified Acute Pain Within 30 Minutes After 13vPnC (Year 5)
    Description Acute pain was not prompted in the electronic diary however were recorded in a specific page of the case report form (CRF). Acute pain at injection site pain occurred within 30 minutes of vaccination and was scaled as: Any (pain present); Mild (easily tolerated); Moderate (discomfort interfering the usual activity); Severe (Incapacitating with inability to do usual activity).
    Time Frame Within 30 Minutes After 13vPnC (Year 5)

    Outcome Measure Data

    Analysis Population Description
    Safety population at Year 5 included all participants who had received at least 1 vaccination and did not lack any safety data.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 364 363
    Acute pain at injection site:Mild
    3.8
    0.7%
    4.4
    0.8%
    Acute pain at injection site:Moderate
    0.3
    0.1%
    0.0
    0%
    Acute pain at injection site:Severe
    0.0
    0%
    0.0
    0%
    Acute pain at injection site: Any
    4.1
    0.7%
    4.4
    0.8%
    30. Other Pre-specified Outcome
    Title Percentage of Participants With Serious Adverse Events (SAEs) or Non-serious Adverse Events (Non-SAEs)
    Description AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Non-serious AEs are AEs excluding SAEs. In Years 1-4, only deaths and withdrawals due to AEs or SAEs were to be recorded in the case report form.
    Time Frame Signing of informed consent up to 194 days after re-vaccination at Year 5

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had received at least 1 vaccination and did not lack any safety data. Here, n=number of participants with known values.
    Arm/Group Title 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5)
    Arm/Group Description Participants received 0.5 milliliter (mL) dose of 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, 13vPnC+TIV). Placebo matched to 13vPnC was administered 1 month after (Dose 2, placebo). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants received placebo matched to 13-valent pneumococcal conjugate vaccine (13vPnC) intramuscular injection into the deltoid muscle of the left arm along with 0.5-mL trivalent inactivated influenza vaccine (TIV) intramuscular injection into the deltoid muscle of the right arm at Year 0 on Day 1 (Dose 1, placebo+TIV). 13vPnC was administered 1 month after (Dose 2, 13vPnC). Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety. Participants were then followed-up yearly for 4 years. Participants then received 0.5 mL dose of 13vPnC intramuscular injection into the deltoid muscle of the left arm 5 years after initial vaccination. Participants were further followed-up for 1 month, then attended a 6-month follow-up visit for safety.
    Measure Participants 551 560
    SAEs at Dose 1 (Year 0) (n=551,560)
    0.7
    0.1%
    0.9
    0.2%
    SAEs at Dose 2 (Year 0) (n=538,543)
    0.6
    0.1%
    1.1
    0.2%
    SAEs at 6-month follow-up (Year 0) (n=538,543)
    3.3
    0.6%
    1.8
    0.3%
    SAEs at Years 1-4(n=536,542)
    1.5
    0.3%
    0.6
    0.1%
    SAEs at 13vPnC (Year 5)(n=364,363)
    0.5
    0.1%
    0.6
    0.1%
    SAEs at 6-month follow-up (Year 5)(n=364,363)
    0.5
    0.1%
    0.5
    0.1%
    non-SAEs at Dose 1 (Year 0)(n=551,560)
    0.5
    0.1%
    0.8
    0.1%
    non-SAEs at Dose 2 (Year 0)(n=538,543)
    16.2
    2.9%
    13.2
    2.4%
    non-SAEs at 6-month follow-up (Year 0)(n=538,543)
    11.3
    2.1%
    10.9
    1.9%
    non-SAEs at Years 1-4(n=536,542)
    0.2
    0%
    0.0
    0%
    non-SAEs at 13vPnC (Year 5)(n=364,363)
    4.7
    0.9%
    3.6
    0.6%
    non-SAEs at 6-month follow-up (Year 5)(n=364,363)
    0.3
    0.1%
    68.3
    12.2%

    Adverse Events

    Time Frame AEs/SAEs recorded: All AEs for 1 month postvaccination. All SAEs and newly diagnosed chronic medical conditions for 6 months postvaccination. Deaths and withdrawals due to S/AE in Years 1-4
    Adverse Event Reporting Description SAEs and AEs were grouped by system organ class and summarized. AEs included AEs collected in electronic diary (local,systemic reactions for 13vPnC; systematic assessment) and AEs collected on case report form at each visit (nonsystematic assessment). Participants who received specified dose and had safety data available were evaluable for safety.
    Arm/Group Title 13vPnC+TIV/Placebo: Dose 1 (Year 0) 13vPnC+TIV/Placebo: Dose 2 (Year 0) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) 13vPnC+TIV/Placebo: Years 1-4 13vPnC+TIV/Placebo: 13vPnC (Year 5) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) Placebo+TIV/13vPnC: Dose 1 (Year 0) Placebo+TIV/13vPnC: Dose 2 (Year 0) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 0) Placebo+TIV/13vPnC: Years 1-4 Placebo+TIV/13vPnC: 13vPnC (Year 5) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 5)
    Arm/Group Description Participants who received 0.5-mL dose of 13vPnC along with 0.5-mL TIV at Year 0 on Day 1 (Dose 1), were assessed for 1 month after Dose 1. Participants who received 0.5-mL Placebo matched to 13vPnC 1 month after Dose 1 (Dose 2), were assessed for 1 month after Dose 2. Participants who received 0.5-mL dose of 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL Placebo matched to 13vPnC 1 month after, were assessed at the 6-month follow-up visit. Participants who received 0.5-mL dose of 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL Placebo matched to 13vPnC 1 month after, were assessed from 6-month follow-up visit at Year 0 to revaccination with 13vPnC given at Year 5. Participants who received 0.5-mL dose of 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL Placebo matched to 13vPnC 1 month after, then 0.5 mL dose of 13vPnC 5 years after initial vaccination, were assessed for 1 month after 13vPnC given at Year 5. Participants who received 0.5-mL dose of 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL Placebo matched to 13vPnC 1 month after, then 0.5 mL dose of 13vPnC 5 years after initial vaccination, were assessed at the 6-month follow-up visit. Participants who received 0.5-mL Placebo matched to 13vPnC along with 0.5-mL TIV at Year 0 on Day 1 (Dose 1), were assessed for 1 month after Dose 1. Participants who received 0.5-mL dose of 13vPnC 1 month after Dose 1 (Dose 2), were assessed for 1 month after Dose 2. Participants who received 0.5-mL Placebo matched to 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL dose of 13vPnC 1 month after, were assessed at the 6-month follow-up visit. Participants who received 0.5-mL Placebo matched to 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL dose of 13vPnC 1 month after, were assessed from 6-month follow-up visit at Year 0 to revaccination with 13vPnC given at Year 5. Participants who received 0.5-mL Placebo matched to 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL dose of 13vPnC 1 month after, then 0.5 mL dose of 13vPnC 5 years after initial vaccination, were assessed for 1 month after 13vPnC given at Year 5. Participants who received 0.5-mL Placebo matched to 13vPnC along with 0.5-mL TIV at Year 0 on Day 1, then 0.5-mL dose of 13vPnC 1 month after, then 0.5 mL dose of 13vPnC 5 years after initial vaccination, were assessed at the 6-month follow-up visit.
    All Cause Mortality
    13vPnC+TIV/Placebo: Dose 1 (Year 0) 13vPnC+TIV/Placebo: Dose 2 (Year 0) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) 13vPnC+TIV/Placebo: Years 1-4 13vPnC+TIV/Placebo: 13vPnC (Year 5) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) Placebo+TIV/13vPnC: Dose 1 (Year 0) Placebo+TIV/13vPnC: Dose 2 (Year 0) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 0) Placebo+TIV/13vPnC: Years 1-4 Placebo+TIV/13vPnC: 13vPnC (Year 5) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    13vPnC+TIV/Placebo: Dose 1 (Year 0) 13vPnC+TIV/Placebo: Dose 2 (Year 0) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) 13vPnC+TIV/Placebo: Years 1-4 13vPnC+TIV/Placebo: 13vPnC (Year 5) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) Placebo+TIV/13vPnC: Dose 1 (Year 0) Placebo+TIV/13vPnC: Dose 2 (Year 0) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 0) Placebo+TIV/13vPnC: Years 1-4 Placebo+TIV/13vPnC: 13vPnC (Year 5) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/551 (0.7%) 3/538 (0.6%) 18/538 (3.3%) 8/536 (1.5%) 2/364 (0.5%) 2/364 (0.5%) 5/560 (0.9%) 6/543 (1.1%) 10/543 (1.8%) 3/542 (0.6%) 2/363 (0.6%) 3/363 (0.8%)
    Cardiac disorders
    Cardiac failure congestive 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 1/542 (0.2%) 0/363 (0%) 0/363 (0%)
    Coronary artery disease 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Myocardial infarction 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 2/536 (0.4%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Palpitations 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ventricular fibrillation 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 1/542 (0.2%) 0/363 (0%) 0/363 (0%)
    Gastrointestinal disorders
    Abdominal mass 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Abdominal pain 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Small intestinal obstruction 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gastrointestinal haemorrhage 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ileus 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Large intestine perforation 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Small intestinal obstruction 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    General disorders
    Non-cardiac chest pain 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Infections and infestations
    Appendicitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Diverticulitis 0/551 (0%) 0/538 (0%) 2/538 (0.4%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Abdominal abscess 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cellulitis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pelvic abscess 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Peridiverticular abscess 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Tuberculosis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Clostridium difficile infection 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Injury, poisoning and procedural complications
    Thermal burn 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Overdose 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Investigations
    Blood glucose increased 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Back pain 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Musculoskeletal chest pain 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Osteoarthritis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 1/363 (0.3%)
    Arthritis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 1/364 (0.3%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rotator cuff syndrome 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Spinal column stenosis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Arthralgia 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Neck pain 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Spinal column stenosis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Basal cell carcinoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Prostate cancer 0/551 (0%) 0/538 (0%) 2/538 (0.4%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 1/363 (0.3%)
    Breast cancer 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Leiomyosarcoma 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Lung neoplasm malignant 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Malignant melanoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Bone cancer 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 1/542 (0.2%) 0/363 (0%) 0/363 (0%)
    Lung cancer metastatic 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Metastatic malignant melanoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pancreatic carcinoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Plasma cell myeloma 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Renal cell carcinoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 1/542 (0.2%) 0/363 (0%) 0/363 (0%)
    Thyroid cancer metastatic 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Colon cancer 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 1/364 (0.3%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Nervous system disorders
    Hepatic encephalopathy 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Syncope 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cerebrovascular accident 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Transient ischaemic attack 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Psychiatric disorders
    Anxiety 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Depression 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Renal and urinary disorders
    Renal colic 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 1/363 (0.3%)
    Reproductive system and breast disorders
    Uterine prolapse 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Haemoptysis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Vascular disorders
    Thrombosis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Other (Not Including Serious) Adverse Events
    13vPnC+TIV/Placebo: Dose 1 (Year 0) 13vPnC+TIV/Placebo: Dose 2 (Year 0) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) 13vPnC+TIV/Placebo: Years 1-4 13vPnC+TIV/Placebo: 13vPnC (Year 5) 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) Placebo+TIV/13vPnC: Dose 1 (Year 0) Placebo+TIV/13vPnC: Dose 2 (Year 0) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 0) Placebo+TIV/13vPnC: Years 1-4 Placebo+TIV/13vPnC: 13vPnC (Year 5) Placebo+TIV/13vPnC: 6 Month Follow-up (Year 5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 420/551 (76.2%) 248/538 (46.1%) 26/538 (4.8%) 1/536 (0.2%) 256/364 (70.3%) 1/364 (0.3%) 326/560 (58.2%) 388/543 (71.5%) 29/543 (5.3%) 0/542 (0%) 248/363 (68.3%) 0/363 (0%)
    Blood and lymphatic system disorders
    Anaemia 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Anaemia macrocytic 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cardiac disorders
    Bundle branch block right 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Coronary artery disease 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Extrasystoles 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Sinus bradycardia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ear and labyrinth disorders
    Cerumen impaction 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Vertigo 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 2/363 (0.6%) 0/363 (0%)
    Endocrine disorders
    Hyperparathyroidism 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Eye disorders
    Abnormal sensation in eye 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Conjunctivitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Eye irritation 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Eye swelling 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Glaucoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ocular hyperaemia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gastrointestinal disorders
    Abdominal hernia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Abdominal pain 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Abdominal pain lower 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Coeliac disease 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Diarrhoea 3/551 (0.5%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Diverticulum 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dyspepsia 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Food poisoning 0/551 (0%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gastrooesophageal reflux disease 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Glossodynia 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Haemorrhoids 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hiatus hernia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Intestinal obstruction 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Irritable bowel syndrome 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Nausea 3/551 (0.5%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 4/560 (0.7%) 4/543 (0.7%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rectal fissure 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rectal polyp 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Stomatitis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Umbilical hernia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Vomiting 2/551 (0.4%) 3/538 (0.6%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    General disorders
    Aggravated generalized joint pain: any 62/292 (21.2%) 41/264 (15.5%) 0/538 (0%) 0/536 (0%) 38/218 (17.4%) 0/364 (0%) 51/284 (18%) 67/282 (23.8%) 0/543 (0%) 0/542 (0%) 39/214 (18.2%) 0/363 (0%)
    Aggravated generalized muscle pain: any 109/314 (34.7%) 50/268 (18.7%) 0/538 (0%) 0/536 (0%) 72/241 (29.9%) 0/364 (0%) 71/294 (24.1%) 112/305 (36.7%) 0/543 (0%) 0/542 (0%) 61/223 (27.4%) 0/363 (0%)
    Any systemic event 417/484 (86.2%) 248/381 (65.1%) 0/538 (0%) 0/536 (0%) 221/307 (72%) 0/364 (0%) 326/430 (75.8%) 326/425 (76.7%) 0/543 (0%) 0/542 (0%) 218/290 (75.2%) 0/363 (0%)
    Chills 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 3/543 (0.6%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Chills: any 96/306 (31.4%) 56/273 (20.5%) 0/538 (0%) 0/536 (0%) 53/229 (23.1%) 0/364 (0%) 61/291 (21%) 68/276 (24.6%) 0/543 (0%) 0/542 (0%) 48/217 (22.1%) 0/363 (0%)
    Cyst 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Decreased appetite: any 95/315 (30.2%) 55/270 (20.4%) 0/538 (0%) 0/536 (0%) 46/226 (20.4%) 0/364 (0%) 68/301 (22.6%) 72/279 (25.8%) 0/543 (0%) 0/542 (0%) 50/227 (22%) 0/363 (0%)
    Fatigue 1/551 (0.2%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 4/560 (0.7%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Fatigue: any 226/389 (58.1%) 138/316 (43.7%) 0/538 (0%) 0/536 (0%) 115/263 (43.7%) 0/364 (0%) 188/359 (52.4%) 175/338 (51.8%) 0/543 (0%) 0/542 (0%) 115/251 (45.8%) 0/363 (0%)
    Fever: > 40.0 degrees C 0/261 (0%) 1/237 (0.4%) 0/538 (0%) 0/536 (0%) 2/205 (1%) 0/364 (0%) 1/257 (0.4%) 0/240 (0%) 0/543 (0%) 0/542 (0%) 3/204 (1.5%) 0/363 (0%)
    Fever: 38.0 to 38.5 degrees C 4/261 (1.5%) 3/238 (1.3%) 0/538 (0%) 0/536 (0%) 2/205 (1%) 0/364 (0%) 3/259 (1.2%) 3/241 (1.2%) 0/543 (0%) 0/542 (0%) 5/206 (2.4%) 0/363 (0%)
    Fever: 38.5 to 39.0 degrees C 4/262 (1.5%) 3/239 (1.3%) 0/538 (0%) 0/536 (0%) 1/206 (0.5%) 0/364 (0%) 0/257 (0%) 2/240 (0.8%) 0/543 (0%) 0/542 (0%) 4/204 (2%) 0/363 (0%)
    Fever: 39.0 to 40.0 degrees C 1/261 (0.4%) 1/236 (0.4%) 0/538 (0%) 0/536 (0%) 0/205 (0%) 0/364 (0%) 0/257 (0%) 1/240 (0.4%) 0/543 (0%) 0/542 (0%) 0/202 (0%) 0/363 (0%)
    Headache: any 263/399 (65.9%) 161/334 (48.2%) 0/538 (0%) 0/536 (0%) 120/256 (46.9%) 0/364 (0%) 216/382 (56.5%) 172/338 (50.9%) 0/543 (0%) 0/542 (0%) 127/248 (51.2%) 0/363 (0%)
    Influenza like illness 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Injection site erythema 3/551 (0.5%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 2/364 (0.5%) 0/364 (0%) 3/560 (0.5%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site haematoma 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site haemorrhage 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site movement impairment 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site nodule 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site pain 2/551 (0.4%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site pruritus 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injection site swelling 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 2/364 (0.5%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Malaise 1/551 (0.2%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    New joint pain: any 102/309 (33%) 55/268 (20.5%) 0/538 (0%) 0/536 (0%) 42/219 (19.2%) 0/364 (0%) 73/296 (24.7%) 78/285 (27.4%) 0/543 (0%) 0/542 (0%) 48/219 (21.9%) 0/363 (0%)
    New muscle pain: any 252/385 (65.5%) 82/288 (28.5%) 0/538 (0%) 0/536 (0%) 127/266 (47.7%) 0/364 (0%) 123/326 (37.7%) 207/350 (59.1%) 0/543 (0%) 0/542 (0%) 129/253 (51%) 0/363 (0%)
    Non-cardiac chest pain 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pain 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 4/560 (0.7%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pyrexia 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rash: any 35/278 (12.6%) 15/246 (6.1%) 0/538 (0%) 0/536 (0%) 16/209 (7.7%) 0/364 (0%) 13/264 (4.9%) 24/252 (9.5%) 0/543 (0%) 0/542 (0%) 29/210 (13.8%) 0/363 (0%)
    Vessel puncture site reaction 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Vomiting: any 14/266 (5.3%) 17/247 (6.9%) 0/538 (0%) 0/536 (0%) 7/206 (3.4%) 0/364 (0%) 9/262 (3.4%) 15/247 (6.1%) 0/543 (0%) 0/542 (0%) 15/207 (7.2%) 0/363 (0%)
    Acute pain at injection site (Mild) 37/551 (6.7%) 32/538 (5.9%) 0/538 (0%) 0/536 (0%) 14/364 (3.8%) 0/364 (0%) 35/560 (6.3%) 35/543 (6.4%) 0/543 (0%) 0/542 (0%) 16/363 (4.4%) 0/363 (0%)
    Acute Pain at injection site (Moderate) 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Acute Pain at injection site (Severe) 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Acute Pain at injection site (Any) 37/551 (6.7%) 32/538 (5.9%) 0/538 (0%) 0/536 (0%) 15/364 (4.1%) 0/364 (0%) 35/560 (6.3%) 35/543 (6.4%) 0/543 (0%) 0/542 (0%) 16/363 (4.4%) 0/363 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cholelithiasis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Immune system disorders
    Seasonal allergy 0/551 (0%) 1/538 (0.2%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Infections and infestations
    Acute sinusitis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Bacterial infection 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Bronchitis 2/551 (0.4%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cellulitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Diverticulitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ear infection 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gastroenteritis 4/551 (0.7%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gastroenteritis viral 3/551 (0.5%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 2/560 (0.4%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Influenza 2/551 (0.4%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 1/543 (0.2%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Laryngitis 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Localised infection 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Lower respiratory tract infection 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Nasopharyngitis 7/551 (1.3%) 4/538 (0.7%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 5/560 (0.9%) 3/543 (0.6%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Otitis media 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pharyngitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pharyngitis streptococcal 1/551 (0.2%) 0/538 (0%) 2/538 (0.4%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pneumonia 1/551 (0.2%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Post procedural infection 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rash pustular 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rhinitis 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Sinusitis 3/551 (0.5%) 1/538 (0.2%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 4/560 (0.7%) 6/543 (1.1%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Staphylococcal infection 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Tooth abscess 2/551 (0.4%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Tuberculosis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Upper respiratory tract infection 4/551 (0.7%) 7/538 (1.3%) 0/538 (0%) 0/536 (0%) 7/364 (1.9%) 0/364 (0%) 4/560 (0.7%) 5/543 (0.9%) 0/543 (0%) 0/542 (0%) 5/363 (1.4%) 0/363 (0%)
    Urinary tract infection 1/551 (0.2%) 1/538 (0.2%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Viral infection 0/551 (0%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Contusion 1/551 (0.2%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Epicondylitis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Fall 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Foot fracture 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Joint injury 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Limb injury 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Lower limb fracture 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 1/364 (0.3%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Muscle strain 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Post procedural haemorrhage 0/551 (0%) 0/538 (0%) 0/538 (0%) 1/536 (0.2%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rib fracture 1/551 (0.2%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Upper limb fracture 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Wrist fracture 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Investigations
    Blood creatinine increased 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Blood glucose increased 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Blood pressure increased 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Heart rate increased 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hepatic enzyme increased 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    International normalised ratio decreased 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Diabetes mellitus 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Gout 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hyperglycaemia 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hyperlipidaemia 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hypoglycaemia 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Impaired fasting glucose 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/551 (0.4%) 3/538 (0.6%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Arthritis 1/551 (0.2%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Back pain 4/551 (0.7%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Bursitis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Fibromyalgia 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Intervertebral disc degeneration 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Intervertebral disc protrusion 1/551 (0.2%) 2/538 (0.4%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Joint swelling 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Mobility decreased 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Musculoskeletal pain 3/551 (0.5%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Musculoskeletal stiffness 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Myalgia 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Neck pain 1/551 (0.2%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Osteoporosis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pain in extremity 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rheumatoid arthritis 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rotator cuff syndrome 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Synovial cyst 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Systemic lupus erythematosus 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Temporomandibular joint syndrome 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Morton's neuroma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Squamous cell carcinoma 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Nervous system disorders
    Carpal tunnel syndrome 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cervicobrachial syndrome 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dizziness 3/551 (0.5%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 1/560 (0.2%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dysgeusia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Headache 1/551 (0.2%) 4/538 (0.7%) 0/538 (0%) 0/536 (0%) 2/364 (0.5%) 0/364 (0%) 8/560 (1.4%) 5/543 (0.9%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Migraine 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Presyncope 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Syncope 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Psychiatric disorders
    Anxiety 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Depression 1/551 (0.2%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Insomnia 2/551 (0.4%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Renal and urinary disorders
    Renal failure 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Renal failure chronic 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Reproductive system and breast disorders
    Breast mass 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Epididymitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Erectile dysfunction 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Prostatitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Atelectasis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Chronic obstructive pulmonary disease 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Cough 5/551 (0.9%) 2/538 (0.4%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 4/560 (0.7%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dysphonia 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dyspnoea 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Epistaxis 1/551 (0.2%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Nasal congestion 3/551 (0.5%) 3/538 (0.6%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 8/560 (1.4%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Oropharyngeal pain 3/551 (0.5%) 3/538 (0.6%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 5/560 (0.9%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Postnasal drip 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Productive cough 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Respiratory disorder 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Rhinitis allergic 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rhinorrhoea 4/551 (0.7%) 3/538 (0.6%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 7/560 (1.3%) 3/543 (0.6%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Sinus congestion 2/551 (0.4%) 4/538 (0.7%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 4/560 (0.7%) 3/543 (0.6%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Sleep apnoea syndrome 1/551 (0.2%) 0/538 (0%) 2/538 (0.4%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Sneezing 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Throat irritation 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Skin and subcutaneous tissue disorders
    Any local reaction 420/474 (88.6%) 105/300 (35%) 0/538 (0%) 0/536 (0%) 256/315 (81.3%) 0/364 (0%) 128/325 (39.4%) 388/456 (85.1%) 0/543 (0%) 0/542 (0%) 248/308 (80.5%) 0/363 (0%)
    Dermatitis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dermatitis contact 2/551 (0.4%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Dry skin 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Erythema 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hyperhidrosis 0/551 (0%) 1/538 (0.2%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 2/543 (0.4%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Ingrowing nail 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Limitation of arm movement: Any 113/317 (35.6%) 23/248 (9.3%) 0/538 (0%) 0/536 (0%) 54/233 (23.2%) 0/364 (0%) 24/270 (8.9%) 135/318 (42.5%) 0/543 (0%) 0/542 (0%) 59/224 (26.3%) 0/363 (0%)
    Limitation of arm movement: Mild 101/310 (32.6%) 23/248 (9.3%) 0/538 (0%) 0/536 (0%) 52/233 (22.3%) 0/364 (0%) 22/268 (8.2%) 130/316 (41.1%) 0/543 (0%) 0/542 (0%) 50/219 (22.8%) 0/363 (0%)
    Limitation of arm movement: Moderate 14/269 (5.2%) 1/236 (0.4%) 0/538 (0%) 0/536 (0%) 6/208 (2.9%) 0/364 (0%) 3/259 (1.2%) 13/248 (5.2%) 0/543 (0%) 0/542 (0%) 8/206 (3.9%) 0/363 (0%)
    Limitation of arm movement: Severe 9/266 (3.4%) 0/236 (0%) 0/538 (0%) 0/536 (0%) 4/206 (1.9%) 0/364 (0%) 2/258 (0.8%) 7/244 (2.9%) 0/543 (0%) 0/542 (0%) 7/206 (3.4%) 0/363 (0%)
    Onychoclasis 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Pain: Any 407/469 (86.8%) 94/294 (32%) 0/538 (0%) 0/536 (0%) 248/313 (79.2%) 0/364 (0%) 119/321 (37.1%) 383/453 (84.5%) 0/543 (0%) 0/542 (0%) 243/306 (79.4%) 0/363 (0%)
    Pain: Mild 380/459 (82.8%) 89/290 (30.7%) 0/538 (0%) 0/536 (0%) 227/297 (76.4%) 0/364 (0%) 112/318 (35.2%) 354/431 (82.1%) 0/543 (0%) 0/542 (0%) 224/299 (74.9%) 0/363 (0%)
    Pain: Moderate 127/324 (39.2%) 11/243 (4.5%) 0/538 (0%) 0/536 (0%) 81/248 (32.7%) 0/364 (0%) 11/261 (4.2%) 131/319 (41.1%) 0/543 (0%) 0/542 (0%) 82/235 (34.9%) 0/363 (0%)
    Pain: Severe 11/267 (4.1%) 0/236 (0%) 0/538 (0%) 0/536 (0%) 9/206 (4.4%) 0/364 (0%) 1/258 (0.4%) 12/248 (4.8%) 0/543 (0%) 0/542 (0%) 7/205 (3.4%) 0/363 (0%)
    Rash 1/551 (0.2%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 2/560 (0.4%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 1/363 (0.3%) 0/363 (0%)
    Rash papular 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Rash pruritic 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 1/560 (0.2%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Redness: Any 46/282 (16.3%) 4/238 (1.7%) 0/538 (0%) 0/536 (0%) 34/216 (15.7%) 0/364 (0%) 8/263 (3%) 31/257 (12.1%) 0/543 (0%) 0/542 (0%) 45/215 (20.9%) 0/363 (0%)
    Redness: Mild 44/281 (15.7%) 4/238 (1.7%) 0/538 (0%) 0/536 (0%) 30/215 (14%) 0/364 (0%) 7/262 (2.7%) 26/255 (10.2%) 0/543 (0%) 0/542 (0%) 37/212 (17.5%) 0/363 (0%)
    Redness: Moderate 11/265 (4.2%) 0/236 (0%) 0/538 (0%) 0/536 (0%) 15/210 (7.1%) 0/364 (0%) 1/258 (0.4%) 14/248 (5.6%) 0/543 (0%) 0/542 (0%) 26/211 (12.3%) 0/363 (0%)
    Redness: Severe 1/262 (0.4%) 0/236 (0%) 0/538 (0%) 0/536 (0%) 3/205 (1.5%) 0/364 (0%) 0/257 (0%) 3/242 (1.2%) 0/543 (0%) 0/542 (0%) 1/202 (0.5%) 0/363 (0%)
    Skin lesion 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 1/543 (0.2%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Swelling: Any 53/288 (18.4%) 11/242 (4.5%) 0/538 (0%) 0/536 (0%) 42/224 (18.8%) 0/364 (0%) 8/263 (3%) 39/265 (14.7%) 0/543 (0%) 0/542 (0%) 39/216 (18.1%) 0/363 (0%)
    Swelling: Mild 49/288 (17%) 11/242 (4.5%) 0/538 (0%) 0/536 (0%) 39/223 (17.5%) 0/364 (0%) 8/263 (3%) 32/260 (12.3%) 0/543 (0%) 0/542 (0%) 34/214 (15.9%) 0/363 (0%)
    Swelling: Moderate 15/263 (5.7%) 1/236 (0.4%) 0/538 (0%) 0/536 (0%) 15/211 (7.1%) 0/364 (0%) 0/257 (0%) 16/249 (6.4%) 0/543 (0%) 0/542 (0%) 20/208 (9.6%) 0/363 (0%)
    Swelling: Severe 1/262 (0.4%) 0/236 (0%) 0/538 (0%) 0/536 (0%) 0/205 (0%) 0/364 (0%) 0/257 (0%) 1/241 (0.4%) 0/543 (0%) 0/542 (0%) 2/203 (1%) 0/363 (0%)
    Social circumstances
    Menopause 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 1/543 (0.2%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Vascular disorders
    Deep vein thrombosis 1/551 (0.2%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Flushing 0/551 (0%) 0/538 (0%) 1/538 (0.2%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Hypertension 0/551 (0%) 0/538 (0%) 3/538 (0.6%) 0/536 (0%) 1/364 (0.3%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 2/543 (0.4%) 0/542 (0%) 0/363 (0%) 0/363 (0%)
    Skin and subcutaneous tissue disorder 0/551 (0%) 0/538 (0%) 0/538 (0%) 0/536 (0%) 0/364 (0%) 0/364 (0%) 0/560 (0%) 0/543 (0%) 0/543 (0%) 0/542 (0%) 0/363 (0%) 0/363 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00521586
    Other Study ID Numbers:
    • 6115A1-3001
    • B1851020
    First Posted:
    Aug 28, 2007
    Last Update Posted:
    Apr 9, 2015
    Last Verified:
    Apr 1, 2015