Immune Response & Safety of a Hepatitis A Vaccine Given Together With a Pneumococcal Vaccine in Healthy Children 15 m of Age

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00197002
• Collaborator: (none)
• Enrollment: 521
• Locations: 18
• Arms: 3
• Actual Duration (Months): 28.2
• Patients Per Site: 28.9
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a study to evaluate the immunogenicity and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a pneumococcal conjugate vaccine in children as young as 15 months of age.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis A	Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix); Biological: Prevnar™	Phase 3

Detailed Description

An open, controlled comparison of Havrix administered alone or with Prevnar. The three groups evaluated are: 1) Havrix alone, 2) Havrix plus Prevnar and 3) Prevnar followed by Havrix one month later.

Study Design

• Study Type: Interventional
• Actual Enrollment: 521 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase IIIb, Open, Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine Administered on a 0-6 Mth Schedule Concomitantly With Wyeth Lederle's Pneumococcal Conjugate Vaccine in Healthy Children 15 Months of Age
• Actual Study Start Date: Sep 11, 2003
• Actual Primary Completion Date: Jan 16, 2006
• Actual Study Completion Date: Jan 16, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Havrix Group Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix); Two doses, administered intramuscularly in the right anterolateral thigh.
Experimental: Havrix+Prevnar Group Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix); Two doses, administered intramuscularly in the right anterolateral thigh.; Biological: Prevnar™; One dose, administered intramuscularly in the left anterolateral thigh.
Active Comparator: Prevnar Havrix Group Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.	Biological: GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix); Two doses, administered intramuscularly in the right anterolateral thigh.; Biological: Prevnar™; One dose, administered intramuscularly in the left anterolateral thigh.

Outcome Measures

Primary Outcome Measures

1. Number of Seropositive Subjects for Anti-HAV Antibodies [At one month after Dose 2 of Havrix® vaccine (Month 7-10)]

   Cut-off values assessed were greater than or equal to (≥) 15 milli-international units per milliliter (mIU/mL) in the sera of subjects seronegative before vaccination.

2. Concentrations for Anti-HAV Antibodies [At one month after Dose 2 of Havrix® vaccine (Month 7-10)]

   Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).

Secondary Outcome Measures

1. Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-19F and Anti-23F Antibody Concentrations [At one month after Prevnar™ vaccination (Day 30)]

   Antibody concentrations against pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL).

2. Number of Subjects With an Immune Response to Anti-pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F [At one month after Prevnar™ vaccination (Day 30)]

   The immune response was defined, with respect to anti-pneumococcal response rates, as an antibody concentration equal to or above (≥) 0.05 μg/mL.

3. Number of Seropositive Subjects for Anti-HAV Antibodies [At one month after Dose 1 of Havrix® vaccine (Day 30)]

   Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination.

4. Concentrations for Anti-HAV Antibodies [At one month after Dose 1 of Havrix® vaccine (Day 30)]

   Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).

5. Number of Seropositive Subjects for Anti-HAV Antibodies [At one month after Dose 2 of Havrix® vaccine (Month 8-11)]

   Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination.

6. Concentrations for Anti-HAV Antibodies [At one month after Dose 2 of Havrix® vaccine (Month 8-11)]

   Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).

7. Number of Subjects With Vaccine Response to Anti-HAV Antibodies [One month after Dose 2 of Havrix® vaccine (Month 7-10/8-10)]

   The vaccine response was defined as: a detectable anti-HAV antibody concentration one month after Dose 2 in subjects who were initially seronegative (antibody concentrations < 15 mIU/mL for anti-HAV); or a 2-fold increase above the pre-vaccination concentration one month after Dose 2 in subjects who were initially seropositive (antibody concentrations ≥ 15 mIU/mL for anti-HAV).

8. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses]

   Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.

9. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses]

   Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination.

10. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [During the 31-day (Day 0-30) follow-up period]

    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

11. Number of Subjects With Serious Adverse Events (SAEs), New Chronic Illnesses (NCIs) and Medically Significant Events (MSEs) [During the Active Phase (from Day 0 to Day 30 after final vaccine dose for each subject)]

    SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

12. Number of Subjects With SAEs, NCIs and MSEs [During the Extended Safety Follow-up (ESFU) Phase (from Day 30 to 6 months after final vaccine dose)]

    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 13 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A male or female child 12 or 13 months of age at the time of entry into the Enrollment Phase,

• Free of obvious health problems,

• Subjects must have previously received three doses of Prevnar in his/her first year of life.

Exclusion Criteria:

• Use of any investigational or non-registered drug or vaccine within 42 days preceding the first dose of study vaccine, or planned use during the study period,

• Chronic administration of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period. (For corticosteroids, this will mean prednisone, or equivalent, less than 0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.),

• Administration of the ACIP-recommended fourth dose of Prevnar prior to entering the Enrollment Phase of the study,

• Planned administration or administration of any vaccine not foreseen by the study protocol within the period of 42 days before and 30 days after each dose of study vaccine(s),

• Previous vaccination against hepatitis A,

• History of hepatitis A or known exposure to hepatitis A,

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection,

• A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection,

• History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of Havrix (e.g., neomycin, 2-phenoxyethanol) or Prevnar (e.g., diphtheria toxoid),

• Major congenital defects or serious chronic illness,

• History of any neurologic disorder (history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject),

• Acute disease, defined as the presence of a moderate or severe illness with or without fever, at the time of vaccination,

• Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Centennial	Colorado	United States	80112
2	GSK Investigational Site	Bardstown	Kentucky	United States	40004
3	GSK Investigational Site	Louisville	Kentucky	United States	40202
4	GSK Investigational Site	Boston	Massachusetts	United States	02115
5	GSK Investigational Site	Boston	Massachusetts	United States	02118
6	GSK Investigational Site	Kalamazoo	Michigan	United States	49008
7	GSK Investigational Site	Omaha	Nebraska	United States	68131
8	GSK Investigational Site	Las Vegas	Nevada	United States	89014
9	GSK Investigational Site	North Las Vegas	Nevada	United States	89025
10	GSK Investigational Site	Stony Brook	New York	United States	11794
11	GSK Investigational Site	Chapel Hill	North Carolina	United States	27514
12	GSK Investigational Site	University Heights	Ohio	United States	44118
13	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15241
14	GSK Investigational Site	Dallas	Texas	United States	75235
15	GSK Investigational Site	San Antonio	Texas	United States	78205-2489
16	GSK Investigational Site	Salt Lake City	Utah	United States	84109
17	GSK Investigational Site	Salt Lake City	Utah	United States	84121
18	GSK Investigational Site	Vancouver	Washington	United States	98664

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Trofa AF, Levin M, Marchant CD, Hedrick J, Blatter MM. Immunogenicity and safety of an inactivated hepatitis a vaccine administered concomitantly with a pneumococcal conjugate vaccine in healthy children 15 months of age. Pediatr Infect Dis J. 2008 Jul;27(7):658-60. doi: 10.1097/INF.0b013e31816907bd.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00197002
• Other Study ID Numbers: 208109/220
• First Posted: Sep 20, 2005
• Last Update Posted: Aug 6, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Pre-assignment Detail	Out of a total of 521 subjects enrolled, 88 subjects were not administered a study vaccine dose and thus were not considered to have started the study.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Period Title: Overall Study
STARTED	147	137	149
COMPLETED	125	119	132
NOT COMPLETED	22	18	17

Baseline Characteristics

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group	Total
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.	Total of all reporting groups
Overall Participants	147	137	149	433
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	15.0 (0.16)	15.0 (0.09)	15.0 (0.24)	15.0 (0.18)
Sex: Female, Male (Count of Participants)
Female	77 52.4%	66 48.2%	79 53%	222 51.3%
Male	70 47.6%	71 51.8%	70 47%	211 48.7%

Outcome Measures

1. Primary Outcome

Title	Number of Seropositive Subjects for Anti-HAV Antibodies
Description	Cut-off values assessed were greater than or equal to (≥) 15 milli-international units per milliliter (mIU/mL) in the sera of subjects seronegative before vaccination.
Time Frame	At one month after Dose 2 of Havrix® vaccine (Month 7-10)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.
Measure Participants	106	94
Count of Participants [Participants]	106 72.1%	94 68.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Havrix Group, Havrix+Prevnar Group
	Comments	Difference in seropositivity rates for anti-HAV: To demonstrate the non-inferiority of Havrix® vaccine co-administered with Prevnar™ vaccine (Havrix+Prevnar Group), compared to Havrix® vaccine administered alone (Havrix Group), in terms of seropositivity rates and geometric mean concentrations (GMCs) for anti-HAV antibody, one month after Dose 2 of Havrix® vaccine (Month 7-10).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The two-sided standardized asymptotic 95% confidence interval (CI) for the difference in seropositivity rates [Havrix+Prevnar Group minus Havrix Group] was computed. The anti-HAV seropositivity rates in the Havrix+Prevnar Group were considered as non-inferior to the seropositivity rates in the Havrix Group, if the lower limit of the 95% CI was not lower (≥) than -5%. The non-inferiority was concluded if both non-inferiority criteria (for seropositivity rates and GMCs) were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in seropositivity rate
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -5.78 to 2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Concentrations for Anti-HAV Antibodies
Description	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).
Time Frame	At one month after Dose 2 of Havrix® vaccine (Month 7-10)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.
Measure Participants	106	94
Geometric Mean (95% Confidence Interval) [mIU/mL]	1609.9	1526.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Havrix Group, Havrix+Prevnar Group
	Comments	To demonstrate the non-inferiority of Havrix® vaccine co-administered with Prevnar™ vaccine (Havrix+Prevnar Group), compared to Havrix® vaccine administered alone (Havrix Group), in terms of seropositivity rates and geometric mean concentrations (GMCs) for anti-HAV antibody, one month after Dose 2 of Havrix® vaccine (Month 7-10).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The standardized two-sided 95% CI for the GMC ratio (Havrix+Prevnar Group divided by Havrix Group) was computed. The anti-HAV GMC in the Havrix+Prevnar Group was considered as non-inferior to the anti-HAV GMC in the Havrix Group if the lower limit of the 95% CI was not lower than (≥) 0.5. The non-inferiority of the anti-HAV immune response in Havrix+Prevnar Group compared to Havrix Group was concluded if both non-inferiority criteria (for seropositivity rates and GMCs) were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMC ratio
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-19F and Anti-23F Antibody Concentrations
Description	Antibody concentrations against pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL).
Time Frame	At one month after Prevnar™ vaccination (Day 30)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	102	117
Anti-4	3.3	3.1
Anti-6B	7.1	6.1
Anti-9V	6.8	7.4
Anti-14	9.8	11.2
Anti-18C	5.8	5.7
Anti-19F	2.8	2.6
Anti-23F	9.0	7.9

4. Secondary Outcome

Title	Number of Subjects With an Immune Response to Anti-pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F
Description	The immune response was defined, with respect to anti-pneumococcal response rates, as an antibody concentration equal to or above (≥) 0.05 μg/mL.
Time Frame	At one month after Prevnar™ vaccination (Day 30)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	102	117
Anti-4	102 69.4%	115 83.9%
Anti-6B	100 68%	115 83.9%
Anti-9V	101 68.7%	116 84.7%
Anti-14	101 68.7%	116 84.7%
Anti-18C	101 68.7%	114 83.2%
Anti-19F	101 68.7%	116 84.7%
Anti-23F	100 68%	115 83.9%

5. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-HAV Antibodies
Description	Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination.
Time Frame	At one month after Dose 1 of Havrix® vaccine (Day 30)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.
Measure Participants	119	103
Count of Participants [Participants]	100 68%	91 66.4%

6. Secondary Outcome

Title	Concentrations for Anti-HAV Antibodies
Description	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).
Time Frame	At one month after Dose 1 of Havrix® vaccine (Day 30)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.
Measure Participants	119	103
Geometric Mean (95% Confidence Interval) [mIU/mL]	48.0	61.0

7. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-HAV Antibodies
Description	Cut-off values assessed were greater than or equal to (≥) 15 mIU/mL in the sera of subjects seronegative before vaccination.
Time Frame	At one month after Dose 2 of Havrix® vaccine (Month 8-11)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	115
Count of Participants [Participants]	113 76.9%

8. Secondary Outcome

Title	Concentrations for Anti-HAV Antibodies
Description	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).
Time Frame	At one month after Dose 2 of Havrix® vaccine (Month 8-11)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP Cohort for Immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	115
Geometric Mean (95% Confidence Interval) [mIU/mL]	1391.2

9. Secondary Outcome

Title	Number of Subjects With Vaccine Response to Anti-HAV Antibodies
Description	The vaccine response was defined as: a detectable anti-HAV antibody concentration one month after Dose 2 in subjects who were initially seronegative (antibody concentrations < 15 mIU/mL for anti-HAV); or a 2-fold increase above the pre-vaccination concentration one month after Dose 2 in subjects who were initially seropositive (antibody concentrations ≥ 15 mIU/mL for anti-HAV).
Time Frame	One month after Dose 2 of Havrix® vaccine (Month 7-10/8-10)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all vaccinated subjects for whom immunogenicity data were available and who complied with the eligibility criteria as defined in the protocol.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	102	90	112
Count of Participants [Participants]	102 69.4%	89 65%	110 73.8%

10. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Time Frame	During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one study vaccine administration documented and with the symptoms sheet filled in.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	141	133	142
Any Pain, Dose 1	39 26.5%	48 35%	61 40.9%
Grade 3 Pain, Dose 1	0 0%	2 1.5%	1 0.7%
Any Redness, Dose 1	31 21.1%	54 39.4%	64 43%
Grade 3 Redness, Dose 1	0 0%	7 5.1%	7 4.7%
Any Swelling, Dose 1	9 6.1%	39 28.5%	38 25.5%
Grade 3 Swelling, Dose 1	0 0%	5 3.6%	2 1.3%
Any Pain, Dose 2	34 23.1%	34 24.8%	35 23.5%
Grade 3 Pain, Dose 2	0 0%	1 0.7%	1 0.7%
Any Redness, Dose 2	30 20.4%	28 20.4%	37 24.8%
Grade 3 Redness, Dose 2	0 0%	1 0.7%	0 0%
Any Swelling, Dose 2	12 8.2%	18 13.1%	17 11.4%
Grade 3 Swelling, Dose 2	0 0%	1 0.7%	0 0%
Any Pain, Dose 3	NA NaN	NA NaN	29 19.5%
Grade 3 Pain, Dose 3	NA NaN	NA NaN	0 0%
Any Redness, Dose 3	NA NaN	NA NaN	32 21.5%
Grade 3 Redness, Dose 3	NA NaN	NA NaN	0 0%
Any Swelling, Dose 3	NA NaN	NA NaN	16 10.7%
Grade 3 Swelling, Dose 3	NA NaN	NA NaN	0 0%
Any Pain, Across Doses	57 38.8%	62 45.3%	76 51%
Grade 3 Pain, Across Doses	0 0%	3 2.2%	2 1.3%
Any Redness, Across Doses	45 30.6%	64 46.7%	78 52.3%
Grade 3 Redness, Across Doses	0 0%	8 5.8%	7 4.7%
Any Swelling, Across Doses	19 12.9%	47 34.3%	48 32.2%
Grade 3 Swelling, Across Doses	0 0%	6 4.4%	2 1.3%

11. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one study vaccine administration documented and with the symptoms sheet filled in.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	141	133	142
Any Drowsiness, Dose 1	40 27.2%	35 25.5%	45 30.2%
Grade 3 Drowsiness, Dose 1	2 1.4%	2 1.5%	3 2%
Related Drowsiness, Dose 1	34 23.1%	34 24.8%	39 26.2%
Any Fever, Dose 1	12 8.2%	19 13.9%	23 15.4%
Grade 3 Fever, Dose 1	0 0%	1 0.7%	2 1.3%
Related Fever, Dose 1	11 7.5%	11 8%	18 12.1%
Any Irritability, Dose 1	48 32.7%	47 34.3%	58 38.9%
Grade 3 Irritability, Dose 1	0 0%	0 0%	2 1.3%
Related Irritability, Dose 1	44 29.9%	44 32.1%	50 33.6%
Any Loss of appetite, Dose 1	36 24.5%	33 24.1%	35 23.5%
Grade 3 Loss of appetite, Dose 1	1 0.7%	2 1.5%	2 1.3%
Related Loss of appetite, Dose 1	31 21.1%	24 17.5%	27 18.1%
Any Drowsiness, Dose 2	18 12.2%	27 19.7%	28 18.8%
Grade 3 Drowsiness, Dose 2	0 0%	2 1.5%	0 0%
Related Drowsiness, Dose 2	16 10.9%	25 18.2%	25 16.8%
Any Fever, Dose 2	12 8.2%	7 5.1%	10 6.7%
Grade 3 Fever, Dose 2	1 0.7%	1 0.7%	2 1.3%
Related Fever, Dose 2	12 8.2%	6 4.4%	7 4.7%
Any Irritability, Dose 2	28 19%	36 26.3%	42 28.2%
Grade 3 Irritability, Dose 2	1 0.7%	0 0%	1 0.7%
Related Irritability, Dose 2	26 17.7%	34 24.8%	40 26.8%
Any Loss of appetite, Dose 2	15 10.2%	20 14.6%	24 16.1%
Grade 3 Loss of appetite, Dose 2	1 0.7%	2 1.5%	0 0%
Related Loss of appetite, Dose 2	14 9.5%	17 12.4%	21 14.1%
Any Drowsiness, Dose 3	NA NaN	NA NaN	20 13.4%
Grade 3 Drowsiness, Dose 3	NA NaN	NA NaN	0 0%
Related Drowsiness, Dose 3	NA NaN	NA NaN	18 12.1%
Any Fever, Dose 3	NA NaN	NA NaN	10 6.7%
Grade 3 Fever, Dose 3	NA NaN	NA NaN	1 0.7%
Related Fever, Dose 3	NA NaN	NA NaN	9 6%
Any Irritability, Dose 3	NA NaN	NA NaN	27 18.1%
Grade 3 Irritability, Dose 3	NA NaN	NA NaN	0 0%
Related Irritability, Dose 3	NA NaN	NA NaN	27 18.1%
Any Loss of appetite, Dose 3	NA NaN	NA NaN	16 10.7%
Grade 3 Loss of appetite, Dose 3	NA NaN	NA NaN	1 0.7%
Related Loss of appetite, Dose 3	NA NaN	NA NaN	14 9.4%
Any Drowsiness, Across	48 32.7%	49 35.8%	63 42.3%
Grade 3 Drowsiness, Across	2 1.4%	4 2.9%	6 4%
Related Drowsiness, Across	41 27.9%	47 34.3%	58 38.9%
Any Fever, Across	21 14.3%	24 17.5%	31 20.8%
Grade 3 Fever, Across	1 0.7%	2 1.5%	4 2.7%
Related Fever, Across	20 13.6%	17 12.4%	26 17.4%
Any Irritability, Across	60 40.8%	65 47.4%	82 55%
Grade 3 Irritability, Across	1 0.7%	0 0%	3 2%
Related Irritability, Across	55 37.4%	63 46%	79 53%
Any Loss of appetite, Across	42 28.6%	45 32.8%	54 36.2%
Grade 3 Loss of appetite, Across	2 1.4%	4 2.9%	3 2%
Related Loss of appetite, Across	37 25.2%	36 26.3%	49 32.9%

12. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Description	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Time Frame	During the 31-day (Day 0-30) follow-up period

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one study vaccine administration documented.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	147	137	149
Any AE(s)	82 55.8%	72 52.6%	87 58.4%
Grade 3 AE(s)	3 2%	5 3.6%	8 5.4%
Related AE(s)	8 5.4%	8 5.8%	12 8.1%

13. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs), New Chronic Illnesses (NCIs) and Medically Significant Events (MSEs)
Description	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	During the Active Phase (from Day 0 to Day 30 after final vaccine dose for each subject)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with at least one study vaccine administration documented.

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	147	137	149
Any SAE(s)	3 2%	5 3.6%	5 3.4%
Any NCI(s)	NA NaN	NA NaN	NA NaN
Any MSE(s)	NA NaN	NA NaN	NA NaN

14. Secondary Outcome

Title	Number of Subjects With SAEs, NCIs and MSEs
Description	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	During the Extended Safety Follow-up (ESFU) Phase (from Day 30 to 6 months after final vaccine dose)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ESFU cohort, which included all vaccinated subjects for whom safety data were available during the extended safety follow-up period (from Day 30 up to 6 months after last vaccine dose).

Arm/Group Title	Havrix Group	Havrix+Prevnar Group	Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.	Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
Measure Participants	123	121	132
Any SAE(s)	0 0%	2 1.5%	3 2%
Any NCI(s)	NA NaN	NA NaN	NA NaN
Any MSE(s)	NA NaN	NA NaN	NA NaN

Adverse Events

Time Frame	Solicited local and general AEs: during the 4-day (Day 0-3); Unsolicited AEs: during the 31-day (Day 0-30); SAEs, NCIs and MSEs: during the entire study period(from Month 0 to Month 12-15/13-16).
Arm/Group Title	Havrix Group		Havrix+Prevnar Group		Prevnar Havrix Group
Arm/Group Description	Healthy male or female subjects, 15 months of age, who received Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Day 0 and at Month 6-9.		Healthy male or female subjects, 15 months of age, who received Havrix® and Prevnar™ vaccines co-administered intramuscularly in the right and left anterolateral thighs, respectively, at Day 0 and Havrix® vaccine administered intramuscularly in the right anterolateral thigh, at Month 6-9.		Healthy male or female subjects, 15 months of age, who received Prevnar™ vaccine administered intramuscularly in the left anterolateral thigh, at Day 0 and Havrix® vaccine, administered intramuscularly in the right anterolateral thigh, at Day 30 and at Month 7-10.
All Cause Mortality
	Havrix Group		Havrix+Prevnar Group		Prevnar Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Havrix Group		Havrix+Prevnar Group		Prevnar Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/177 (3.4%)		8/169 (4.7%)		10/175 (5.7%)
Ear and labyrinth disorders
Hearing impaired (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
General disorders
Developmental delay (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
Gait disturbance (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
Infections and infestations
Bronchiolitis (enrollment phase)	1/177 (0.6%)		0/169 (0%)		0/175 (0%)
Gastroenteritis (enrollment phase)	1/177 (0.6%)		0/169 (0%)		0/175 (0%)
Otitis media acute (enrollment phase)	2/177 (1.1%)		0/169 (0%)		0/175 (0%)
Upper respiratory tract infection (enrollment phase)	1/177 (0.6%)		0/169 (0%)		0/175 (0%)
Croup infectious (active phase)	1/147 (0.7%)		1/137 (0.7%)		0/149 (0%)
Pneumonia (active phase)	0/147 (0%)		2/137 (1.5%)		0/149 (0%)
Bronchiolitis (active phase)	0/147 (0%)		0/137 (0%)		1/149 (0.7%)
Gastroenteritis viral	0/147 (0%)		0/137 (0%)		1/149 (0.7%)
Kawasaki's disease (active phase)	1/147 (0.7%)		0/137 (0%)		0/149 (0%)
Gastroenteritis viral (ESFU phase)	0/123 (0%)		1/121 (0.8%)		1/132 (0.8%)
Kawasaki's disease (ESFU phase)	0/123 (0%)		0/121 (0%)		1/132 (0.8%)
Pneumonia (ESFU phase)	0/123 (0%)		1/121 (0.8%)		0/132 (0%)
Injury, poisoning and procedural complications
Burns second degree (enrolllment phase)	0/177 (0%)		0/169 (0%)		1/175 (0.6%)
Metabolism and nutrition disorders
Lactose intolerance (enrollment phase)	0/177 (0%)		0/169 (0%)		1/175 (0.6%)
Dehydration (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
Diabetes mellitus insulin-dependent (active phase)	0/147 (0%)		0/137 (0%)		1/149 (0.7%)
Dehydration (ESFU phase)	0/123 (0%)		0/121 (0%)		2/132 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Langerhans' cell granulomatosis (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
Nervous system disorders
Convulsion (enrollment phase)	1/177 (0.6%)		1/169 (0.6%)		0/175 (0%)
Convulsion (active phase)	1/147 (0.7%)		0/137 (0%)		1/149 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchial hyperactivity (active phase)	0/147 (0%)		0/137 (0%)		1/149 (0.7%)
Hypoxia (active phase)	0/147 (0%)		1/137 (0.7%)		0/149 (0%)
Other (Not Including Serious) Adverse Events
	Havrix Group		Havrix+Prevnar Group		Prevnar Havrix Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/147 (72.8%)		106/137 (77.4%)		121/149 (81.2%)
Gastrointestinal disorders
Diarrhea	8/147 (5.4%)		8/137 (5.8%)		8/149 (5.4%)
General disorders
Pain	57/141 (40.4%)		62/133 (46.6%)		76/142 (53.5%)
Redness	45/141 (31.9%)		64/133 (48.1%)		78/142 (54.9%)
Swelling	19/141 (13.5%)		47/133 (35.3%)		48/142 (33.8%)
Drowsiness	48/141 (34%)		49/133 (36.8%)		63/142 (44.4%)
Fever (Axillary)	21/141 (14.9%)		24/133 (18%)		31/142 (21.8%)
Irritability	60/141 (42.6%)		65/133 (48.9%)		82/142 (57.7%)
Loss of appetite	42/141 (29.8%)		45/133 (33.8%)		54/142 (38%)
Pyrexia	10/147 (6.8%)		8/137 (5.8%)		12/149 (8.1%)
Infections and infestations
Upper respiratory tract infection	22/147 (15%)		17/137 (12.4%)		26/149 (17.4%)
Otitis media	14/147 (9.5%)		20/137 (14.6%)		27/149 (18.1%)
Respiratory, thoracic and mediastinal disorders
Cough	7/147 (4.8%)		5/137 (3.6%)		8/149 (5.4%)
Rhinorrhea	1/147 (0.7%)		3/137 (2.2%)		13/149 (8.7%)

Limitations/Caveats

None reported.

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.