Study Evaluating 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Healthy Children Aged 15 Months to 17 Years

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00761631
• Collaborator: (none)
• Enrollment: 1,200
• Locations: 31
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 38.7
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This open-label, multicenter study is designed to evaluate the safety, tolerability and immunogenicity of 13-valent pneumococcal conjugate vaccine in healthy children aged more than 15 months up to less than 18 years.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 1200 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Open Label Trial Evaluating the Safety,Tolerability and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Healthy Children Aged 15 Months to 17 Years in the United States
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Open label	Biological: 13 valent pneumococcal conjugate vaccine; Intramuscular injection of 0.5mL at visit 1 and visit 2 for group 1 and and visit 1 for groups 2, 3, and 4.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Predefined Serotype-specific Immunoglobulin G (IgG) Antibody Concentration Greater Than or Equal to (≥) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After Vaccination in Group 1 and 2 [28 to 42 days after dose 2 for Group 1 and 28 to 42 days after dose 1 for Group 2]

   Percentage of participants achieving world health organization (WHO) predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were presented. Exact 2-sided CI based on observed proportion of participants.

2. Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Measured 1 Month After Vaccination in Group 3 [28 to 42 days after dose 1 for Group 3]

   Antibody GMC for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were presented. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for after dose 1 blood draw.

3. Comparison of Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Measured 1 Month After 13vPnC Vaccination in Group 3 Relative to Posttoddler Responses in Study 6096A1-3005 (NCT00444457) [28 to 42 days after dose 1]

   Comparison of IgG concentrations 1 month after 13vPnC vaccination in group 3 of study 6096A1-3011 (NCT00761631) to posttoddler responses in 7-valent pneumococcal conjugate vaccine (7vPnC) group for 7 common serotypes and in combined 13vPnC groups for 6 additional serotypes of study 6096A1-3005 (NCT00444457) is not reported here because analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in study and described in Participant Flow and Baseline Characteristics modules.

4. Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After Vaccination in Group 3 and 4 [28 to 42 days after dose 1 for Group 3 and 4]

   Serotype-specific OPA GMTs for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were determined in the blood samples of all the participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all participants with available data for after dose 1 blood draw.

Other Outcome Measures

1. Percentage of Participants Reporting Prespecified Local Reactions Within 7 Days of Dose 1 [From the day of dose 1 (Day 1) to Day 7 after dose 1]

   Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm).

2. Percentage of Participants Reporting Prespecified Local Reactions Within 7 Days of Dose 2 [From the day of dose 2 (Day 1) to Day 7 of dose 2]

   Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm).

3. Percentage of Participants Reporting Prespecified Systemic Events Within 7 Days of Dose 1 [From the day of dose 1 (Day 1) to Day 7 of dose 1]

   Systemic events (any fever >=38 degrees [deg] Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary.

4. Percentage of Participants Reporting Prespecified Systemic Events Within 7 Days of Dose 2 [From the day of dose 2 (Day 1) to Day 7 of dose 2]

   Systemic events (any fever >=38 deg C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may have been represented in more than 1 category. Percentage of participants = number of participants reporting specified systemic event divided by number of participants reporting yes for at least 1 day or no for all days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female subjects >15months to <18years in good health, available for entire study period and reachable by phone, parents/legal guardian able and willing to complete all study procedures, written documentation from health professional showing prior vaccination with Prevnar (except for group 4).

Group 4 only:

• Negative urine pregnancy test for female subjects who are menstruating.

Exclusion Criteria:

• Previous reaction or contra-indication to pneumococcal vaccine or vaccine related component , bleeding diathesis, received blood transfusion or blood related products, immune deficiency,congenital malformation.

Group 4 only:

• Previous vaccination with Prevnar or any other pneumococcal vaccine.

• Pregnant or breastfeeding adolescent females.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Benton	Arkansas	United States	72019
2	Pfizer Investigational Site	Fayetteville	Arkansas	United States	72703
3	Pfizer Investigational Site	Jonesboro	Arkansas	United States	72401
4	Pfizer Investigational Site	Little Rock	Arkansas	United States	72205
5	Pfizer Investigational Site	Fountain Valley	California	United States	92708
6	Pfizer Investigational Site	Loma Linda	California	United States	92354
7	Pfizer Investigational Site	Torrance	California	United States	90502
8	Pfizer Investigational Site	Tampa	Florida	United States	33606
9	Pfizer Investigational Site	Marietta	Georgia	United States	30062
10	Pfizer Investigational Site	Dekalb	Illinois	United States	60115
11	Pfizer Investigational Site	Louisville	Kentucky	United States	40202-3830
12	Pfizer Investigational Site	St.Paul	Minnesota	United States	55108
13	Pfizer Investigational Site	Lebanon	New Hampshire	United States	03756
14	Pfizer Investigational Site	Whitehouse Station	New Jersey	United States	08809
15	Pfizer Investigational Site	Rochester	New York	United States	14618
16	Pfizer Investigational Site	Cary	North Carolina	United States	27518
17	Pfizer Investigational Site	Bismarck	North Dakota	United States	58501
18	Pfizer Investigational Site	Fargo	North Dakota	United States	58103
19	Pfizer Investigational Site	Cincinnati	Ohio	United States	45229
20	Pfizer Investigational Site	Cleveland	Ohio	United States	44121
21	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74127
22	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19107
23	Pfizer Investigational Site	Clarksville	Tennessee	United States	37043
24	Pfizer Investigational Site	Galveston	Texas	United States	77555-0351
25	Pfizer Investigational Site	San Antonio	Texas	United States	78229
26	Pfizer Investigational Site	Murray	Utah	United States	84107
27	Pfizer Investigational Site	Salt Lake City	Utah	United States	84132
28	Pfizer Investigational Site	South Jordan	Utah	United States	84095
29	Pfizer Investigational Site	Vienna	Virginia	United States	22180
30	Pfizer Investigational Site	Vancouver	Washington	United States	98664
31	Pfizer Investigational Site	Monroe	Wisconsin	United States	53566

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00761631
• Other Study ID Numbers: 6096A1-3011
• First Posted: Sep 29, 2008
• Last Update Posted: Jul 31, 2013
• Last Verified: May 1, 2013

• Additional relevant MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Pre-assignment Detail	Participants were stratified by age group. Group 1 included participants aged greater than (>) 15 months to less than (<) 2 years. Group 2 included participants aged greater than or equal to (>=) 2 to <5 years. Group 3 included participants aged >=5 to <10 years. Group 4 included participants aged >=10 to <18 years.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 2 (Cohort 1)	13vPnC Group 1 (Cohort 2)	13vPnC Group 2 (Cohort 2)	13vPnC Group 3	13vPnC Group 4
Arm/Group Description	13-valent pneumococcal conjugate vaccine (13vPnC) 0.5 milliliter (mL) dose administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7-valent pneumococcal conjugate vaccine (7vPnC). Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.
Period Title: Overall Study
STARTED	126	181	176	119	299	299
Vaccinated Dose 1	124	179	175	118	294	298
Vaccinated Dose 2	112	0	165	0	0	0
COMPLETED	111	174	160	116	277	294
NOT COMPLETED	15	7	16	3	22	5

Baseline Characteristics

Arm/Group Title	13vPnC Group 1 (Cohort 1 and 2)	13vPnC Group 2 (Cohort 1 and 2)	13vPnC Group 3	13vPnC Group 4	Total
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to and after protocol amendment to increase sample size (Cohort 1 and Cohort 2, combined)	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to and after protocol amendment to increase sample size (Cohort 1 and Cohort 2, combined)	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.	Total of all reporting groups
Overall Participants	302	300	299	299	1200
Age, Customized (Number) [Number]
>15 months to <2 years	302 100%	0 0%	0 0%	0 0%	302 25.2%
>=2 years to <5 years	0 0%	300 100%	0 0%	0 0%	300 25%
>=5 years to <10 years	0 0%	0 0%	299 100%	0 0%	299 24.9%
>10 years to <18 years	0 0%	0 0%	0 0%	299 100%	299 24.9%
Sex: Female, Male (Count of Participants)
Female	148 49%	139 46.3%	155 51.8%	136 45.5%	578 48.2%
Male	154 51%	161 53.7%	144 48.2%	163 54.5%	622 51.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Predefined Serotype-specific Immunoglobulin G (IgG) Antibody Concentration Greater Than or Equal to (≥) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After Vaccination in Group 1 and 2
Description	Percentage of participants achieving world health organization (WHO) predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were presented. Exact 2-sided CI based on observed proportion of participants.
Time Frame	28 to 42 days after dose 2 for Group 1 and 28 to 42 days after dose 1 for Group 2

Outcome Measure Data

Analysis Population Description

Evaluable Immunogenicity Population (EIP): all participants who met all inclusion criteria, received all assigned doses of study vaccine, had at least 1 valid and determinate assay result from blood draw within 27-56 days after last scheduled vaccination for proposed analysis and no major protocol violations.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 2 (Cohort 1)
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).
Measure Participants	109	175
Common serotypes - serotype 4	98.2 32.5%	100.0 33.3%
Common serotypes - serotype 6B	100.0 33.1%	100.0 33.3%
Common serotypes - serotype 9V	100.0 33.1%	100.0 33.3%
Common serotypes - serotype 14	100.0 33.1%	100.0 33.3%
Common serotypes - serotype 18C	100.0 33.1%	100.0 33.3%
Common serotypes - serotype 19F	100.0 33.1%	100.0 33.3%
Common serotypes - serotype 23F	99.1 32.8%	100.0 33.3%
Additional serotypes - serotype 1	100.0 33.1%	98.9 33%
Additional serotypes - serotype 3	94.5 31.3%	92.0 30.7%
Additional serotypes - serotype 5	100.0 33.1%	98.9 33%
Additional serotypes - serotype 6A	100.0 33.1%	100.0 33.3%
Additional serotypes - serotype 7F	100.0 33.1%	100.0 33.3%
Additional serotypes - serotype 19A	100.0 33.1%	100.0 33.3%

2. Primary Outcome

Title	Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Measured 1 Month After Vaccination in Group 3
Description	Antibody GMC for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were presented. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for after dose 1 blood draw.
Time Frame	28 to 42 days after dose 1 for Group 3

Outcome Measure Data

Analysis Population Description

EIP: participants who met all inclusion criteria, received all assigned doses of study vaccine;had at least 1 valid, determinate assay result from blood draw within 27-56 days after last scheduled vaccination for proposed analysis;no major protocol violations. N (number of participants analyzed)=participants with determinate antibody concentration.

Arm/Group Title	13vPnC Group 3
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.
Measure Participants	171
Common serotypes - serotype 4	8.45
Common serotypes - serotype 6B	53.56
Common serotypes - serotype 9V	9.51
Common serotypes - serotype 14	29.36
Common serotypes - serotype 18C	8.23
Common serotypes - serotype 19F	17.58
Common serotypes - serotype 23F	11.26
Additional serotypes - serotype 1	3.57
Additional serotypes - serotype 3	2.38
Additional serotypes - serotype 5	5.52
Additional serotypes - serotype 6A	21.51
Additional serotypes - serotype 7F	6.24
Additional serotypes - serotype 19A	17.18

3. Primary Outcome

Title	Comparison of Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Measured 1 Month After 13vPnC Vaccination in Group 3 Relative to Posttoddler Responses in Study 6096A1-3005 (NCT00444457)
Description	Comparison of IgG concentrations 1 month after 13vPnC vaccination in group 3 of study 6096A1-3011 (NCT00761631) to posttoddler responses in 7-valent pneumococcal conjugate vaccine (7vPnC) group for 7 common serotypes and in combined 13vPnC groups for 6 additional serotypes of study 6096A1-3005 (NCT00444457) is not reported here because analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in study and described in Participant Flow and Baseline Characteristics modules.
Time Frame	28 to 42 days after dose 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Primary Outcome

Title	Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After Vaccination in Group 3 and 4
Description	Serotype-specific OPA GMTs for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were determined in the blood samples of all the participants using a microcolony OPA (mcOPA) assay. GMT (13vPnC) and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all participants with available data for after dose 1 blood draw.
Time Frame	28 to 42 days after dose 1 for Group 3 and 4

Outcome Measure Data

Analysis Population Description

EIP: participants who met all inclusion criteria, received all assigned doses of study vaccine;had at least 1 valid, determinate assay result from blood draw within 27-56 days after last scheduled vaccination for proposed analysis;no major protocol violations. N (number of participants analyzed)=participants with a determinate antibody titer.

Arm/Group Title	13vPnC Group 3	13vPnC Group 4
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.
Measure Participants	189	181
Common serotypes - serotype 4	6912	4629
Common serotypes - serotype 6B	14224	14996
Common serotypes - serotype 9V	4485	4733
Common serotypes - serotype 14	6894	4759
Common serotypes - serotype 18C	6263	8815
Common serotypes - serotype 19F	2280	1559
Common serotypes - serotype 23F	3808	3245
Additional serotypes - serotype 1	319	187
Additional serotypes - serotype 3	114	202
Additional serotypes - serotype 5	336	491
Additional serotypes - serotype 6A	9928	7514
Additional serotypes - serotype 7F	6584	10334
Additional serotypes - serotype 19A	1276	1180

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 4: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 1.24 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 6B: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 9V: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 14: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 1.19 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 18C: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; 0.59 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 19F: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 1.15 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 23F: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 1: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 1.36 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 3: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.48 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 5: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; 0.53 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 6A: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 7F: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.53 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	13vPnC Group 1 (Cohort 1), 13vPnC Group 2 (Cohort 1)
	Comments	Serotype 19A: CI for the GMT ratio was calculated by the back transformations of CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC Group 4 - 13vPnC Group 3).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was to be concluded if the lower bound of the 2-sided 95% CI was greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Other Pre-specified Outcome

Title	Percentage of Participants Reporting Prespecified Local Reactions Within 7 Days of Dose 1
Description	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm).
Time Frame	From the day of dose 1 (Day 1) to Day 7 after dose 1

Outcome Measure Data

Analysis Population Description

Dose 1 Safety Population: all participants who received the first dose of 13vPnC. 'N' (number of participants analyzed )=participants with known values for any local reaction. 'n'=number of participants with known values for specified local reaction for each group respectively. Participants may be represented in more than 1 category.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 2 (Cohort 1)	13vPnC Group 1 (Cohort 2)	13vPnC Group 2 (Cohort 2)	13vPnC Group 3	13vPnC Group 4
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.
Measure Participants	110	158	151	102	270	285
Tenderness Any (n=108,155, 148,102,265,283)	50.9 16.9%	61.9 20.6%	45.3 15.2%	62.7 21%	86.8 7.2%	89.0 NaN
Tenderness Significant (n=92,141,133,92,221,242)	7.6 2.5%	10.6 3.5%	5.3 1.8%	13.0 4.3%	19.5 1.6%	43.8 NaN
Swelling Any (n=97,144,142,90,226,233)	25.8 8.5%	22.2 7.4%	17.6 5.9%	20.0 6.7%	37.6 3.1%	36.9 NaN
Swelling Mild (n=94,143,141,89,220,221)	21.3 7.1%	20.3 6.8%	14.2 4.7%	13.5 4.5%	21.8 1.8%	22.6 NaN
Swelling Moderate (n=94,141,135,89,219,226)	9.6 3.2%	5.7 1.9%	7.4 2.5%	11.2 3.7%	21.9 1.8%	21.2 NaN
Swelling Severe (n=90,138,131,88,211,214)	0.0 0%	0.0 0%	0.0 0%	1.1 0.4%	3.3 0.3%	1.9 NaN
Redness Any (n=103,149,143,91,233,232)	39.8 13.2%	34.9 11.6%	18.9 6.3%	36.3 12.1%	42.9 3.6%	30.2 NaN
Redness Mild (n=99,146,143,90,226,226)	31.3 10.4%	31.5 10.5%	16.8 5.6%	31.1 10.4%	27.9 2.3%	21.2 NaN
Redness Moderate (n=94,142,135,89,218,221)	12.8 4.2%	9.9 3.3%	5.9 2%	14.6 4.9%	22.0 1.8%	14.0 NaN
Redness Severe (n=90,138,131,88,212,213)	0.0 0%	0.0 0%	0.8 0.3%	1.1 0.4%	3.3 0.3%	1.9 NaN

6. Other Pre-specified Outcome

Title	Percentage of Participants Reporting Prespecified Local Reactions Within 7 Days of Dose 2
Description	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm).
Time Frame	From the day of dose 2 (Day 1) to Day 7 of dose 2

Outcome Measure Data

Analysis Population Description

Dose 2 Safety Population: all participants who received 2 doses of 13vPnC. 'N' (number of participants analyzed )=participants with known values for any local reaction. 'n'=number of participants with known values for specified local reaction for each group respectively. Participants may be represented in more than 1 category.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 1 (Cohort 2)
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).
Measure Participants	90	131
Tenderness Any (n=87, 125)	57.5 19%	55.2 18.4%
Tenderness Significant (n=68, 101)	8.8 2.9%	9.9 3.3%
Swelling Any (n=73, 105)	23.3 7.7%	17.1 5.7%
Swelling Mild (n=72, 104)	22.2 7.4%	15.4 5.1%
Swelling Moderate (n=69, 102)	2.9 1%	7.8 2.6%
Swelling Severe (n=68, 98)	0.0 0%	0.0 0%
Redness Any (n=76, 110)	35.5 11.8%	23.6 7.9%
Redness Mild (n=74, 108)	33.8 11.2%	18.5 6.2%
Redness Moderate (n=70, 100)	7.1 2.4%	6.0 2%
Redness Severe (n=68, 98)	0.0 0%	0.0 0%

7. Other Pre-specified Outcome

Title	Percentage of Participants Reporting Prespecified Systemic Events Within 7 Days of Dose 1
Description	Systemic events (any fever >=38 degrees [deg] Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary.
Time Frame	From the day of dose 1 (Day 1) to Day 7 of dose 1

Outcome Measure Data

Analysis Population Description

Dose 1 Safety Population: all participants who received the first dose of 13vPnC. 'N' (number of participants analyzed )=participants with known values for any systemic events. 'n'=number of participants with known values for specified systemic events for each group respectively. Participants may be represented in more than 1 category.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 2 (Cohort 1)	13vPnC Group 1 (Cohort 2)	13vPnC Group 2 (Cohort 2)	13vPnC Group 3	13vPnC Group 4
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.
Measure Participants	112	157	165	107	250	253
Fever >=38 to <=39 degC(n=92,138,137,90,212,214)	16.3 5.4%	5.1 1.7%	17.5 5.9%	14.4 4.8%	4.2 0.4%	5.1 NaN
Fever >39 but <=40 degC(n=90,138,130,89,212,212)	4.4 1.5%	0.7 0.2%	4.6 1.5%	3.4 1.1%	2.4 0.2%	0.5 NaN
Fever >40 degC (n=90,138,130,88,210,212)	0.0 0%	0.7 0.2%	0.0 0%	1.1 0.4%	0.5 0%	0.5 NaN
Decreased appetite (n=99,149,146,94,227,223)	42.4 14%	24.8 8.3%	39.7 13.3%	34.0 11.4%	22.9 1.9%	22.9 NaN
Irritability (n=108,151,156,102,234,234)	60.2 19.9%	39.7 13.2%	72.4 24.2%	52.0 17.4%	31.2 2.6%	25.2 NaN
Increased sleep (n=98,145,146,97,226,229)	32.7 10.8%	15.9 5.3%	37.0 12.4%	23.7 7.9%	21.2 1.8%	26.6 NaN
Decreased sleep (n=97,143,140,91,212,224)	22.7 7.5%	14.0 4.7%	32.1 10.7%	18.7 6.3%	5.7 0.5%	18.8 NaN
Hives (urticaria) (n=90,139,131,88,213,214)	1.1 0.4%	0.7 0.2%	1.5 0.5%	4.5 1.5%	1.9 0.2%	1.4 NaN

8. Other Pre-specified Outcome

Title	Percentage of Participants Reporting Prespecified Systemic Events Within 7 Days of Dose 2
Description	Systemic events (any fever >=38 deg C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may have been represented in more than 1 category. Percentage of participants = number of participants reporting specified systemic event divided by number of participants reporting yes for at least 1 day or no for all days.
Time Frame	From the day of dose 2 (Day 1) to Day 7 of dose 2

Outcome Measure Data

Analysis Population Description

Dose 2 Safety Population: all participants who received 2 doses of 13vPnC. 'N' (number of participants analyzed )=participants with known values for any systemic events. 'n'=number of participants with known values for specified systemic events for each group respectively. Participants may be represented in more than 1 category.

Arm/Group Title	13vPnC Group 1 (Cohort 1)	13vPnC Group 1 (Cohort 2)
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).	13vPnC (0.5mL dose) administered intramuscularly at baseline and anytime from Day 56 to Day 70 for a total of 2 doses. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).
Measure Participants	91	137
Fever >=38 but <=39 degC (n=70,101)	14.3 4.7%	11.9 4%
Fever >39 but <=40 degC (n=68, 100)	4.4 1.5%	2.0 0.7%
Fever >40 degC (n=68, 98)	0.0 0%	1.0 0.3%
Decreased appetite (n=77, 113)	40.3 13.3%	34.5 11.5%
Irritability (n=86, 126)	65.1 21.6%	61.1 20.4%
Increased sleep (n=75, 109)	29.3 9.7%	23.9 8%
Decreased sleep (n=77, 112)	28.6 9.5%	26.8 8.9%
Hives (urticaria) (n=68, 98)	2.9 1%	0.0 0%

Adverse Events

Time Frame	Group 1: Baseline up to Day 280; Group 2, 3 and 4: Baseline up to Day 210. Participants recorded pre-specified AEs in electronic diary:local reactions; systemic events (up to 7 days after each vaccine dose)
Adverse Event Reporting Description	SAEs and AEs were grouped by system organ class and summarized. AEs included solicited AEs collected in the electronic diary (local and systemic reactions; systematic assessment) and unsolicited events collected on the case report form at each visit (nonsystematic assessment).
Arm/Group Title	13vPnC Group 1 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 1) Dose 2		13vPnC Group 2 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 2) Dose 1		13vPnC Group 1 (Cohort 2) Dose 2		13vPnC Group 2 (Cohort 2) Dose 1		6-Month Follow-up 13vPnC Group 1 (Cohort 1 and 2)		6-Month Follow-up 13vPnC Group 2 (Cohort 1 and 2)		13vPnC Group 3		6-Month Follow-up 13vPnC Group 3		13vPnC Group 4		6-Month Follow-up 13vPnC Group 4
Arm/Group Description	13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).		13vPnC (0.5mL dose) administered intramuscularly anytime from Day 56 to Day 70. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).		13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled prior to protocol amendment to increase sample size (Cohort 1).		13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).		13vPnC (0.5mL dose) administered intramuscularly anytime from Day 56 to Day 70. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).		13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 3 doses of 7vPnC. Includes participants enrolled after protocol amendment to increase sample size (Cohort 2).		6-month follow-up telephone contact for participants in Group 1 (Cohort 1 and 2).		6-month follow-up telephone contact for participants in Group 2 (Cohort 1 and 2).		13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must have previously received at least 1 dose of 7vPnC.		6-month follow-up telephone contact for participants in Group 3.		13vPnC (0.5mL dose) administered intramuscularly at baseline. Participants must not have received 7vPnC or any other pneumococcal vaccine.		6 -Month Follow-up Telephone Contact for participants in Group 4.
All Cause Mortality
	13vPnC Group 1 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 1) Dose 2		13vPnC Group 2 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 2) Dose 1		13vPnC Group 1 (Cohort 2) Dose 2		13vPnC Group 2 (Cohort 2) Dose 1		6-Month Follow-up 13vPnC Group 1 (Cohort 1 and 2)		6-Month Follow-up 13vPnC Group 2 (Cohort 1 and 2)		13vPnC Group 3		6-Month Follow-up 13vPnC Group 3		13vPnC Group 4		6-Month Follow-up 13vPnC Group 4
	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 Group 1 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 1) Dose 2		13vPnC Group 2 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 2) Dose 1		13vPnC Group 1 (Cohort 2) Dose 2		13vPnC Group 2 (Cohort 2) Dose 1		6-Month Follow-up 13vPnC Group 1 (Cohort 1 and 2)		6-Month Follow-up 13vPnC Group 2 (Cohort 1 and 2)		13vPnC Group 3		6-Month Follow-up 13vPnC Group 3		13vPnC Group 4		6-Month Follow-up 13vPnC Group 4
	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	0/124 (0%)		2/112 (1.8%)		1/179 (0.6%)		1/175 (0.6%)		4/165 (2.4%)		0/118 (0%)		3/299 (1%)		1/297 (0.3%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		1/298 (0.3%)
Gastrointestinal disorders
Vomiting	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		1/299 (0.3%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Infections and infestations
Pneumonia	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Gastroenteritis rotavirus	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Respiratory syncytial virus bronchiolitis	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Bronchiolitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Staphylococcal infection	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Appendicitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Injury, poisoning and procedural complications
Near drowning	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Abdominal injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		1/299 (0.3%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Nervous system disorders
Febrile convulsion	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		1/299 (0.3%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Renal and urinary disorders
Nephrotic syndrome	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		1/299 (0.3%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Respiratory, thoracic and mediastinal disorders
Wheezing	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Asthma	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		1/298 (0.3%)
Status asthmaticus	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		1/297 (0.3%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Other (Not Including Serious) Adverse Events
	13vPnC Group 1 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 1) Dose 2		13vPnC Group 2 (Cohort 1) Dose 1		13vPnC Group 1 (Cohort 2) Dose 1		13vPnC Group 1 (Cohort 2) Dose 2		13vPnC Group 2 (Cohort 2) Dose 1		6-Month Follow-up 13vPnC Group 1 (Cohort 1 and 2)		6-Month Follow-up 13vPnC Group 2 (Cohort 1 and 2)		13vPnC Group 3		6-Month Follow-up 13vPnC Group 3		13vPnC Group 4		6-Month Follow-up 13vPnC Group 4
	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	112/124 (90.3%)		91/112 (81.3%)		158/179 (88.3%)		165/175 (94.3%)		137/165 (83%)		107/118 (90.7%)		2/299 (0.7%)		2/297 (0.7%)		242/294 (82.3%)		7/294 (2.4%)		258/298 (86.6%)		4/298 (1.3%)
Blood and lymphatic system disorders
Anaemia	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Leukocytosis	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Ear and labyrinth disorders
Ear pain	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		3/175 (1.7%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Eustachian tube dysfunction	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Eye disorders
Conjunctivitis	2/124 (1.6%)		4/112 (3.6%)		2/179 (1.1%)		2/175 (1.1%)		3/165 (1.8%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		2/294 (0.7%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Hypermetropia	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Eye swelling	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Lacrimation increased	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Myopia	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		1/294 (0.3%)		0/298 (0%)		0/298 (0%)
Gastrointestinal disorders
Diarrhoea	6/124 (4.8%)		1/112 (0.9%)		4/179 (2.2%)		6/175 (3.4%)		3/165 (1.8%)		2/118 (1.7%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		1/298 (0.3%)		1/298 (0.3%)
Vomiting	7/124 (5.6%)		1/112 (0.9%)		1/179 (0.6%)		2/175 (1.1%)		3/165 (1.8%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		8/294 (2.7%)		0/294 (0%)		4/298 (1.3%)		0/298 (0%)
Abdominal pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		2/165 (1.2%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Constipation	0/124 (0%)		1/112 (0.9%)		1/179 (0.6%)		2/175 (1.1%)		1/165 (0.6%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Lip dry	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Teething	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Tongue coated	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Duodenogastric reflux	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Abdominal pain upper	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Nausea	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		3/298 (1%)		0/298 (0%)
Irritable bowel syndrome	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		1/294 (0.3%)		0/298 (0%)		0/298 (0%)
Toothache	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Uvulitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
General disorders
Pyrexia	5/124 (4%)		3/112 (2.7%)		3/179 (1.7%)		7/175 (4%)		5/165 (3%)		4/118 (3.4%)		0/299 (0%)		0/297 (0%)		7/294 (2.4%)		0/294 (0%)		3/298 (1%)		0/298 (0%)
Influenza like illness	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Injection site reaction	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Injection site pruritus	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Fever >=38 degreesC but <=39 degreesC	15/92 (16.3%)		10/70 (14.3%)		7/138 (5.1%)		24/137 (17.5%)		12/101 (11.9%)		13/90 (14.4%)		0/0 (NaN)		0/0 (NaN)		9/212 (4.2%)		0/0 (NaN)		11/214 (5.1%)		0/0 (NaN)
Fever >39 degreesC but <=40 degreesC	4/90 (4.4%)		3/68 (4.4%)		1/138 (0.7%)		6/130 (4.6%)		2/100 (2%)		3/89 (3.4%)		0/0 (NaN)		0/0 (NaN)		5/212 (2.4%)		0/0 (NaN)		1/212 (0.5%)		0/0 (NaN)
Fever >40 degreesC	0/90 (0%)		0/68 (0%)		1/138 (0.7%)		0/130 (0%)		1/98 (1%)		1/88 (1.1%)		0/0 (NaN)		0/0 (NaN)		1/210 (0.5%)		0/0 (NaN)		1/212 (0.5%)		0/0 (NaN)
Decreased appetite	42/99 (42.4%)		31/77 (40.3%)		37/149 (24.8%)		58/146 (39.7%)		39/113 (34.5%)		32/94 (34%)		0/0 (NaN)		0/0 (NaN)		52/227 (22.9%)		0/0 (NaN)		51/223 (22.9%)		0/0 (NaN)
Irritability	65/108 (60.2%)		56/86 (65.1%)		60/151 (39.7%)		113/156 (72.4%)		77/126 (61.1%)		53/102 (52%)		0/0 (NaN)		0/0 (NaN)		73/234 (31.2%)		0/0 (NaN)		59/234 (25.2%)		0/0 (NaN)
Increased sleep	32/98 (32.7%)		22/75 (29.3%)		23/145 (15.9%)		54/146 (37%)		26/109 (23.9%)		23/97 (23.7%)		0/0 (NaN)		0/0 (NaN)		48/226 (21.2%)		0/0 (NaN)		61/229 (26.6%)		0/0 (NaN)
Decreased sleep	22/97 (22.7%)		22/77 (28.6%)		20/143 (14%)		45/140 (32.1%)		30/112 (26.8%)		17/91 (18.7%)		0/0 (NaN)		0/0 (NaN)		12/212 (5.7%)		0/0 (NaN)		42/224 (18.8%)		0/0 (NaN)
Hives (urticaria)	1/90 (1.1%)		2/68 (2.9%)		1/139 (0.7%)		2/131 (1.5%)		0/98 (0%)		4/88 (4.5%)		0/0 (NaN)		0/0 (NaN)		4/213 (1.9%)		0/0 (NaN)		3/214 (1.4%)		0/0 (NaN)
Chills	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Injection site pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Immune system disorders
Drug hypersensitivity	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Seasonal allergy	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Infections and infestations
Otitis media	15/124 (12.1%)		5/112 (4.5%)		12/179 (6.7%)		12/175 (6.9%)		11/165 (6.7%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Upper respiratory tract infection	9/124 (7.3%)		9/112 (8%)		3/179 (1.7%)		15/175 (8.6%)		14/165 (8.5%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		2/294 (0.7%)		0/294 (0%)		3/298 (1%)		0/298 (0%)
Nasopharyngitis	4/124 (3.2%)		1/112 (0.9%)		1/179 (0.6%)		7/175 (4%)		2/165 (1.2%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		3/298 (1%)		0/298 (0%)
Sinusitis	3/124 (2.4%)		3/112 (2.7%)		4/179 (2.2%)		4/175 (2.3%)		1/165 (0.6%)		2/118 (1.7%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		5/298 (1.7%)		0/298 (0%)
Rhinitis	3/124 (2.4%)		0/112 (0%)		2/179 (1.1%)		8/175 (4.6%)		3/165 (1.8%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Otitis media acute	3/124 (2.4%)		1/112 (0.9%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Viral infection	2/124 (1.6%)		1/112 (0.9%)		5/179 (2.8%)		4/175 (2.3%)		3/165 (1.8%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		4/298 (1.3%)		0/298 (0%)
Croup infectious	2/124 (1.6%)		1/112 (0.9%)		2/179 (1.1%)		7/175 (4%)		1/165 (0.6%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Gastroenteritis	2/124 (1.6%)		0/112 (0%)		2/179 (1.1%)		2/175 (1.1%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Pharyngitis	2/124 (1.6%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		1/165 (0.6%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		2/294 (0.7%)		0/294 (0%)		5/298 (1.7%)		0/298 (0%)
Ear infection	2/124 (1.6%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Gastroenteritis viral	2/124 (1.6%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		2/294 (0.7%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Viral upper respiratory tract infection	1/124 (0.8%)		1/112 (0.9%)		3/179 (1.7%)		2/175 (1.1%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Bronchitis	1/124 (0.8%)		1/112 (0.9%)		1/179 (0.6%)		3/175 (1.7%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Bronchiolitis	1/124 (0.8%)		1/112 (0.9%)		0/179 (0%)		2/175 (1.1%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Eye infection	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Impetigo	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Influenza	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		2/175 (1.1%)		0/165 (0%)		2/118 (1.7%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		5/298 (1.7%)		0/298 (0%)
Lice infestation	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Otitis media chronic	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Paronychia	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Pneumonia viral	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Subcutaneous abscess	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Skin infection	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Tonsillitis	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Urinary tract infection	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Pharyngitis streptococcal	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		2/175 (1.1%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		6/294 (2%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Intertrigo candida	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Otitis externa	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Respiratory syncytial virus infection	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Urethritis	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Viral rash	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Cellulitis streptococcal	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Coxsackie viral infection	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Dermatitis infected	0/124 (0%)		1/112 (0.9%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Erythema infectiosum	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		2/165 (1.2%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Folliculitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Hand-foot-and-mouth disease	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Oral candidiasis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Oral herpes	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Acarodermatitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Dermatophytosis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Viral pharyngitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Acute sinusitis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Furuncle	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Injury, poisoning and procedural complications
Skin laceration	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Excoriation	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Lower limb fracture	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Burns second degree	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Head injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Laceration	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Mouth injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Traumatic brain injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Ulna fracture	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Contusion	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Eye injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Hand fracture	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Periorbital haematoma	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Arthropod bite	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Foot fracture	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Limb injury	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Muscle strain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Procedural pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Wrist fracture	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Investigations
Cardiac murmur	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Heart rate decreased	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Metabolism and nutrition disorders
Anorexia	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Lactose intolerance	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Back pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Neck Pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Torticollis	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Musculoskeletal chest pain	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Nervous system disorders
Headache	1/124 (0.8%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		2/118 (1.7%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		10/298 (3.4%)		0/298 (0%)
Speech disorder developmental	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Presyncope	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Syncope	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Dizziness	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Migraine	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		1/298 (0.3%)
Somnolence	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Psychiatric disorders
Breath holding	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Sleep disorder	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		1/297 (0.3%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Asperger's disorder	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		1/297 (0.3%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Attention deficit/hyperactivity disorder	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		1/297 (0.3%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Anxiety	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Depression	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		1/298 (0.3%)
Renal and urinary disorders
Dysuria	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Haematuria	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Reproductive system and breast disorders
Vulvovaginal discomfort	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Penile adhesion	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	5/124 (4%)		0/112 (0%)		7/179 (3.9%)		6/175 (3.4%)		7/165 (4.2%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		10/294 (3.4%)		0/294 (0%)		5/298 (1.7%)		0/298 (0%)
Rhinorrhoea	5/124 (4%)		2/112 (1.8%)		4/179 (2.2%)		5/175 (2.9%)		4/165 (2.4%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Epistaxis	2/124 (1.6%)		0/112 (0%)		1/179 (0.6%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Nasal congestion	1/124 (0.8%)		1/112 (0.9%)		1/179 (0.6%)		2/175 (1.1%)		2/165 (1.2%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		3/294 (1%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Pneumonitis	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Sinus congestion	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Wheezing	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Asthma	0/124 (0%)		0/112 (0%)		4/179 (2.2%)		0/175 (0%)		1/165 (0.6%)		3/118 (2.5%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		2/294 (0.7%)		2/298 (0.7%)		0/298 (0%)
Oropharyngeal pain	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		1/175 (0.6%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		5/298 (1.7%)		0/298 (0%)
Rhinitis allergic	0/124 (0%)		0/112 (0%)		1/179 (0.6%)		2/175 (1.1%)		1/165 (0.6%)		0/118 (0%)		1/299 (0.3%)		1/297 (0.3%)		0/294 (0%)		1/294 (0.3%)		0/298 (0%)		1/298 (0.3%)
Bronchial hyperreactivity	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		2/294 (0.7%)		0/298 (0%)		0/298 (0%)
Bronchospasm	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Interstitial lung disease	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Paranasal sinus hypersecretion	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Sneezing	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Skin and subcutaneous tissue disorders
Dermatitis diaper	1/124 (0.8%)		1/112 (0.9%)		0/179 (0%)		6/175 (3.4%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Rash	2/124 (1.6%)		2/112 (1.8%)		2/179 (1.1%)		5/175 (2.9%)		0/165 (0%)		1/118 (0.8%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)
Dermatitis atopic	0/124 (0%)		0/112 (0%)		0/179 (0%)		1/175 (0.6%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Eczema	1/124 (0.8%)		2/112 (1.8%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		1/118 (0.8%)		1/299 (0.3%)		0/297 (0%)		1/294 (0.3%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Dermatitis	2/124 (1.6%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Dermatitis contact	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Skin disorder	1/124 (0.8%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Erythema	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Ingrowing nail	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		1/165 (0.6%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		0/298 (0%)		0/298 (0%)
Tenderness (any)	55/108 (50.9%)		50/87 (57.5%)		96/155 (61.9%)		67/148 (45.3%)		69/125 (55.2%)		64/102 (62.7%)		0/0 (NaN)		0/0 (NaN)		230/265 (86.8%)		0/0 (NaN)		252/283 (89%)		0/0 (NaN)
Tenderness (significant)	7/92 (7.6%)		6/68 (8.8%)		15/141 (10.6%)		7/133 (5.3%)		10/101 (9.9%)		12/92 (13%)		0/0 (NaN)		0/0 (NaN)		43/221 (19.5%)		0/0 (NaN)		106/242 (43.8%)		0/0 (NaN)
Swelling (any)	25/97 (25.8%)		17/73 (23.3%)		32/144 (22.2%)		25/142 (17.6%)		18/105 (17.1%)		18/90 (20%)		0/0 (NaN)		0/0 (NaN)		85/226 (37.6%)		0/0 (NaN)		86/233 (36.9%)		0/0 (NaN)
Swelling (mild)	20/94 (21.3%)		16/72 (22.2%)		29/143 (20.3%)		20/141 (14.2%)		16/104 (15.4%)		12/89 (13.5%)		0/0 (NaN)		0/0 (NaN)		48/220 (21.8%)		0/0 (NaN)		50/221 (22.6%)		0/0 (NaN)
Swelling (moderate)	9/94 (9.6%)		2/69 (2.9%)		8/141 (5.7%)		10/135 (7.4%)		8/102 (7.8%)		10/89 (11.2%)		0/0 (NaN)		0/0 (NaN)		48/219 (21.9%)		0/0 (NaN)		48/226 (21.2%)		0/0 (NaN)
Swelling (severe)	0/90 (0%)		0/68 (0%)		0/138 (0%)		0/131 (0%)		0/98 (0%)		1/88 (1.1%)		0/0 (NaN)		0/0 (NaN)		7/211 (3.3%)		0/0 (NaN)		4/214 (1.9%)		0/0 (NaN)
Redness (any)	41/103 (39.8%)		27/76 (35.5%)		52/149 (34.9%)		27/143 (18.9%)		26/110 (23.6%)		33/91 (36.3%)		0/0 (NaN)		0/0 (NaN)		100/233 (42.9%)		0/0 (NaN)		70/232 (30.2%)		0/0 (NaN)
Redness (mild)	31/99 (31.3%)		25/74 (33.8%)		46/146 (31.5%)		24/143 (16.8%)		20/108 (18.5%)		28/90 (31.1%)		0/0 (NaN)		0/0 (NaN)		63/226 (27.9%)		0/0 (NaN)		48/226 (21.2%)		0/0 (NaN)
Redness (moderate)	12/94 (12.8%)		5/70 (7.1%)		14/142 (9.9%)		8/135 (5.9%)		6/100 (6%)		13/89 (14.6%)		0/0 (NaN)		0/0 (NaN)		48/218 (22%)		0/0 (NaN)		31/221 (14%)		0/0 (NaN)
Redness (severe)	0/90 (0%)		0/68 (0%)		0/138 (0%)		1/131 (0.8%)		0/98 (0%)		1/88 (1.1%)		0/0 (NaN)		0/0 (NaN)		7/212 (3.3%)		0/0 (NaN)		4/213 (1.9%)		0/0 (NaN)
Acne	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		2/298 (0.7%)		0/298 (0%)
Acanthosis nigricans	0/124 (0%)		0/112 (0%)		0/179 (0%)		0/175 (0%)		0/165 (0%)		0/118 (0%)		0/299 (0%)		0/297 (0%)		0/294 (0%)		0/294 (0%)		1/298 (0.3%)		0/298 (0%)

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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.