Safety and Immunogenicity of GSK's Tdap Vaccine (Boostrix) in Adults Aged 19 to 64 Years

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00346073
• Collaborator: (none)
• Enrollment: 2,337
• Locations: 42
• Arms: 2
• Actual Duration (Months): 7.8
• Patients Per Site: 55.6
• Patients Per Site Per Month: 7.1

Study Details

Study Description

Brief Summary

GSK Biologicals' dTpa vaccine has recently been approved by the US Food and Drug Administration (FDA) for booster vaccination of adolescents aged 10 to 18 years. The ACIP has recently issued provisional recommendations for universal adult Tdap vaccination. The current study will provide pivotal data in support of extending the age range for Boostrix vaccine to include adults 19-64 years of age.

Condition or Disease	Intervention/Treatment	Phase
Acellular Pertussis; Diphtheria; Tetanus	Biological: Boostrix™; Biological: ADACEL®	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Study to Evaluate Immunogenicity and Safety of Boostrix Compared to Adacel When Administered as a Booster Vaccination in Adults Aged 19 to 64 Years of Age
• Actual Study Start Date: Jul 13, 2006
• Actual Primary Completion Date: Mar 1, 2007
• Actual Study Completion Date: Mar 7, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Boostrix Group Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Biological: Boostrix™; Combined Reduced Antigen Content Diphtheria, Tetanus, Acellular Pertussis Vaccine
Experimental: Adacel Group Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Biological: ADACEL®; Sanofi Pasteur

Outcome Measures

Primary Outcome Measures

1. Number of Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [At Month 1]

   A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to ( ≥) 0.1 international units per milliliter (IU/mL).

2. Number of Seropositive Subjects With Anti-tetanus (Anti-T) Antibodies [At Month 1]

   A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).

3. Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [At Month 1]

   Concentrations are presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

4. Number of Subjects With Booster Responses for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies [At Month 1]

   Booster responses for anti-PT, anti-FHA and anti-PRN antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 5 EU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥) 20 EU/mL), one month after vaccination; for initially seropositive subjects with pre-vaccination concentration ≥ 5 EU/mL and < 20 EU/mL: an increase in antibody concentrations of at least four times the pre-vaccination concentration one month after vaccination; and for initially seropositive subjects with pre-vaccination concentration ≥ 20 EU/mL: an increase in antibody concentrations of at least two times the pre-vaccination concentration, one month after vaccination.

Secondary Outcome Measures

1. Number of Seropositive Subjects With Anti-diphteria (Anti-D) Antibodies [At Month 1]

   A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to (≥) 1.0 international units per milliliter (IU/mL).

2. Number of Subjects With Booster Responses for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) [At Month 1]

   Booster responses for anti-D and anti-T antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 0.1 IU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥ 0.4 IU/mL), one month after vaccination; and for initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration one month after vaccination.

3. Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [At Month 1]

   Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

4. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 15-day period (Day 0-14) following vaccination]

   Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.

5. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 15-day period (Day 0-14) following vaccination]

   Assessed solicited general symptoms were fatigue, fever [defined as temperature measured orally, greater than or equal to (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [gastro sympt.] and headache. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

6. Number of Subjects With Any Unsolicited Adverse Events (AEs) [During the 31-day period (Days 0-30) following vaccination]

   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.

7. Number of Subjects With Serious Adverse Events (SAEs). [During the active phase of the study (Day 0 - Day 30)]

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

8. Number of Subjects With Serious Adverse Events (SAEs) [During the extended safety follow-up (ESFU) phase (Day 31 - Month 6)]

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

9. Number of Subjects Reporting Hospitalizations [During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)]

   Hospitalization signified that the subject had been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out patient setting.

10. Number of Subjects Reporting Emergency Room Visits [During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)]

    Emergency room visits refer to AEs requiring immediate medical attention.

11. Number of Subjects Reporting the Onset of New Chronic Illnesses [During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)]

    New onset chronic illnesses include diabetes, asthma, allergies, autoimmune diseases.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A healthy male or female, 19 to 64 years of age (not having reached the 65th birthday) at the time of study vaccination.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding administration of study vaccine, or planned use during the active phase of the study.

• Chronic administration of immunosuppressants or within six months prior to administration of study vaccine.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of administration of study vaccine (with the exception of an influenza vaccine).

• Administration of a diphtheria-tetanus (Td) booster within previous five years.

• Administration of Tdap vaccine at any time prior to study entry. History of serious allergic reaction (e.g. anaphylaxis) following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine or any component of the study vaccines.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Huntsville	Alabama	United States	35802
2	GSK Investigational Site	Chandler	Arizona	United States	85224
3	GSK Investigational Site	Mesa	Arizona	United States	85203
4	GSK Investigational Site	Mesa	Arizona	United States	85213
5	GSK Investigational Site	Peoria	Arizona	United States	85381 - 4828
6	GSK Investigational Site	Phoenix	Arizona	United States	85014
7	GSK Investigational Site	Tempe	Arizona	United States	85283
8	GSK Investigational Site	Little Rock	Arkansas	United States	72205
9	GSK Investigational Site	San Diego	California	United States	92103-6204
10	GSK Investigational Site	San Diego	California	United States	92108
11	GSK Investigational Site	Colorado Springs	Colorado	United States	80909
12	GSK Investigational Site	Pueblo	Colorado	United States	81001
13	GSK Investigational Site	Washington	District of Columbia	United States	20036
14	GSK Investigational Site	Melbourne	Florida	United States	32901
15	GSK Investigational Site	Miami	Florida	United States	33143
16	GSK Investigational Site	Pembroke Pines	Florida	United States	33024
17	GSK Investigational Site	Tampa	Florida	United States	33603
18	GSK Investigational Site	Boise	Idaho	United States	83713
19	GSK Investigational Site	Peoria	Illinois	United States	61602
20	GSK Investigational Site	South Bend	Indiana	United States	46601
21	GSK Investigational Site	Bardstown	Kentucky	United States	40004
22	GSK Investigational Site	Richland	Michigan	United States	49083
23	GSK Investigational Site	Kansas City	Missouri	United States	64114
24	GSK Investigational Site	Saint Louis	Missouri	United States	63141
25	GSK Investigational Site	Alliance	Nebraska	United States	69301
26	GSK Investigational Site	North Platte	Nebraska	United States	69101
27	GSK Investigational Site	Las Vegas	Nevada	United States	89104
28	GSK Investigational Site	Albuquerque	New Mexico	United States	87108
29	GSK Investigational Site	Hickory	North Carolina	United States	28601
30	GSK Investigational Site	Raleigh	North Carolina	United States	27609
31	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
32	GSK Investigational Site	Bismarck	North Dakota	United States	58501
33	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
34	GSK Investigational Site	Grove City	Pennsylvania	United States	16127
35	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15241
36	GSK Investigational Site	Bristol	Tennessee	United States	37620
37	GSK Investigational Site	Knoxville	Tennessee	United States	37920
38	GSK Investigational Site	Houston	Texas	United States	77024
39	GSK Investigational Site	Salt Lake City	Utah	United States	84109
40	GSK Investigational Site	Salt Lake City	Utah	United States	84121
41	GSK Investigational Site	West Jordan	Utah	United States	84088
42	GSK Investigational Site	Norfolk	Virginia	United States	23507

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

• Blatter M, Friedland LR, Weston WM, Li P, Howe B. Immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19-64 years of age. Vaccine. 2009 Jan 29;27(5):765-72. doi: 10.1016/j.vaccine.2008.11.028. Epub 2008 Nov 27.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00346073
• Other Study ID Numbers: 106316
• First Posted: Jun 29, 2006
• Last Update Posted: Aug 7, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Prophylaxis for diphtheria, tetanus, pertussis; Immunogenicity, booster, dTpa
• Additional relevant MeSH terms: Whooping Cough; Tetanus; Diphtheria

Study Results

Participant Flow

Pre-assignment Detail	A total of 2337 subjects were enrolled into the study. Of these, 53 subjects were allocated subject numbers, but did not receive study vaccination.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Period Title: Overall Study
STARTED	1522	762
COMPLETED	1481	738
NOT COMPLETED	41	24

Baseline Characteristics

Arm/Group Title	Boostrix Group	Adacel Group	Total
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Total of all reporting groups
Overall Participants	1522	762	2284
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.9 (13.64)	40.1 (13.51)	39.97 (13.59)
Sex: Female, Male (Count of Participants)
Female	946 62.2%	479 62.9%	1425 62.4%
Male	576 37.8%	283 37.1%	859 37.6%
Race/Ethnicity, Customized (Count of Participants)
African heritage/African American	126 8.3%	61 8%	187 8.2%
American Indian or Alaskan native	6 0.4%	5 0.7%	11 0.5%
Asian - Central/South Asian heritage	1 0.1%	0 0%	1 0%
Asian - East Asian heritage	2 0.1%	1 0.1%	3 0.1%
Asian - Japanese heritage	3 0.2%	0 0%	3 0.1%
Asian - South East Asian heritage	6 0.4%	3 0.4%	9 0.4%
Native Hawaiian or other Pacific islander	6 0.4%	3 0.4%	9 0.4%
White - Arabic/North African heritage	19 1.2%	13 1.7%	32 1.4%
White - Caucasian/European heritage	1281 84.2%	635 83.3%	1916 83.9%
Not specified	72 4.7%	41 5.4%	113 4.9%

Outcome Measures

1. Primary Outcome

Title	Number of Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies
Description	A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to ( ≥) 0.1 international units per milliliter (IU/mL).
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1445	728
Anti-D	1418 93.2%	717 94.1%
Anti-T	1439 94.5%	728 95.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group, Adacel Group
	Comments	The non-inferiority of Boostrix® vaccine compared to Adacel™ vaccine, with respect to the percentage of subjects with anti-diphtheria (anti-D) antibody concentrations greater than or equal to (≥) 0.1 IU/mL, one month after vaccination.
	Type of Statistical Test	Non-Inferiority
	Comments	The primary objective of non-inferiority was met if the lower limit of the 95% confidence intervals (CIs), between the two groups (Boostrix Group - Adacel Group) were greater than or equal to (≥) -10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.47 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group, Adacel Group
	Comments	The non-inferiority of Boostrix® vaccine compared to Adacel™ vaccine, with respect to the percentage of subjects with anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) 0.1 IU/mL, one month after vaccination.
	Type of Statistical Test	Non-Inferiority
	Comments	The primary objective of non-inferiority was met if the lower limit of the 95% confidence intervals (CIs), between the two groups (Boostrix Group - Adacel Group) were greater than or equal to (≥) -10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Seropositive Subjects With Anti-tetanus (Anti-T) Antibodies
Description	A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1445	728
Count of Participants [Participants]	1420 93.3%	723 94.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group, Adacel Group
	Comments	The non-inferiority of Boostrix® vaccine compared to Adacel™ vaccine, with respect to the percentage of subjects with anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) 1.0 IU/mL, one month after vaccination.
	Type of Statistical Test	Non-Inferiority
	Comments	The primary objective of non-inferiority was met if the lower limit of the 95% confidence intervals (CIs), between the two groups (Boostrix Group - Adacel Group) were greater than or equal to (≥) -10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95%; -1.97 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
Description	Concentrations are presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available. The primary outcome results only refer to subjects who received a Boostrix vaccination.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	726
Anti-PT	63.6	32.2
Anti-FHA	624.4	368.4
Anti-PRN	401.0	351.9

4. Primary Outcome

Title	Number of Subjects With Booster Responses for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies
Description	Booster responses for anti-PT, anti-FHA and anti-PRN antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 5 EU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥) 20 EU/mL), one month after vaccination; for initially seropositive subjects with pre-vaccination concentration ≥ 5 EU/mL and < 20 EU/mL: an increase in antibody concentrations of at least four times the pre-vaccination concentration one month after vaccination; and for initially seropositive subjects with pre-vaccination concentration ≥ 20 EU/mL: an increase in antibody concentrations of at least two times the pre-vaccination concentration, one month after vaccination.
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available. The primary outcome results only refer to subjects who received a Boostrix vaccination.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1441	725
Anti-PT	1095 71.9%	338 44.4%
Anti-FHA	1388 91.2%	671 88.1%
Anti-PRN	1343 88.2%	665 87.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group
	Comments	Demonstration that anti-PT booster response occurred in at least 80% of adults receiving a single dose of Boostrix® vaccine, one month after vaccination. Criterion for evaluation: one month after vaccination, the lower limit of the 95% confidence interval (CI) for the percentage of subjects with a booster response was greater than or equal to (≥) 80%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Booster response
	Estimated Value	77.2
	Confidence Interval	(2-Sided) 95%; 74.9 to 79.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group
	Comments	Demonstration that anti-FHA booster response occurred in at least 80% of adults receiving a single dose of Boostrix® vaccine, one month after vaccination. Criterion for evaluation: one month after vaccination, the lower limit of the 95% confidence interval (CI) for the percentage of subjects with a booster response was greater than or equal to (≥) 80%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Booster response
	Estimated Value	96.9
	Confidence Interval	(2-Sided) 95%; 95.8 to 97.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Boostrix Group
	Comments	Demonstration that anti-PRN booster response occurred in at least 80% of adults receiving a single dose of Boostrix® vaccine, one month after vaccination. Criterion for evaluation: one month after vaccination, the lower limit of the 95% confidence interval (CI) for the percentage of subjects with a booster response was greater than or equal to (≥) 80%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Booster response
	Estimated Value	93.2
	Confidence Interval	(2-Sided) 95%; 91.8 to 94.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Seropositive Subjects With Anti-diphteria (Anti-D) Antibodies
Description	A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to (≥) 1.0 international units per milliliter (IU/mL).
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	727
Count of Participants [Participants]	1269 83.4%	669 87.8%

6. Secondary Outcome

Title	Number of Subjects With Booster Responses for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T)
Description	Booster responses for anti-D and anti-T antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 0.1 IU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥ 0.4 IU/mL), one month after vaccination; and for initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration one month after vaccination.
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	727
Anti-D	1116 73.3%	566 74.3%
Anti-T	704 46.3%	441 57.9%

7. Secondary Outcome

Title	Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time Frame	At Month 1

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1445	728
Anti-D	4.7	5.0
Anti-T	8.5	13.3

8. 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 = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Time Frame	During the 15-day period (Day 0-14) following vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1480	741
Pain, Any	903 59.3%	513 67.3%
Pain, Grade 3	24 1.6%	17 2.2%
Redness, Any	313 20.6%	201 26.4%
Redness, ≥ 50 mm	23 1.5%	17 2.2%
Swelling, Any	260 17.1%	190 24.9%
Swelling, ≥ 50 mm	21 1.4%	21 2.8%

9. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were fatigue, fever [defined as temperature measured orally, greater than or equal to (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [gastro sympt.] and headache. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	During the 15-day period (Day 0-14) following vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1480	741
Fatigue, Any	416 27.3%	214 28.1%
Fatigue, Grade 3	37 2.4%	9 1.2%
Fatigue, Related	251 16.5%	151 19.8%
Fever (orally), ≥37.5 °C	82 5.4%	59 7.7%
Fever (orally), ≥39 °C	1 0.1%	3 0.4%
Fever, Related	40 2.6%	28 3.7%
Gastro sympt., Any	235 15.4%	130 17.1%
Gastro sympt., Grade 3	18 1.2%	10 1.3%
Gastro sympt., Related	125 8.2%	67 8.8%
Headache, Any	445 29.2%	230 30.2%
Headache, Grade 3	32 2.1%	11 1.4%
Headache, Related	245 16.1%	143 18.8%

10. Secondary Outcome

Title	Number of Subjects With Any 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.
Time Frame	During the 31-day period (Days 0-30) following vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1522	762
Count of Participants [Participants]	271 17.8%	169 22.2%

11. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs).
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame	During the active phase of the study (Day 0 - Day 30)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1522	762
Count of Participants [Participants]	9 0.6%	2 0.3%

12. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame	During the extended safety follow-up (ESFU) phase (Day 31 - Month 6)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Extended Safety Follow Up (ESFU) cohort, which included all the subjects for whom the ESFU contact was completed. Two subjects were not contacted after the active phase of study, but had SAEs reported in the ESFU period.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1445	719
Count of Participants [Participants]	12 0.8%	11 1.4%

13. Secondary Outcome

Title	Number of Subjects Reporting Hospitalizations
Description	Hospitalization signified that the subject had been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out patient setting.
Time Frame	During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Extended Safety Follow Up (ESFU) cohort, which included all the subjects for whom the ESFU contact was completed.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	718
Count of Participants [Participants]	13 0.9%	10 1.3%

14. Secondary Outcome

Title	Number of Subjects Reporting Emergency Room Visits
Description	Emergency room visits refer to AEs requiring immediate medical attention.
Time Frame	During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Extended Safety Follow Up (ESFU) cohort, which included all the subjects for whom the ESFU contact was completed.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	718
Count of Participants [Participants]	13 0.9%	6 0.8%

15. Secondary Outcome

Title	Number of Subjects Reporting the Onset of New Chronic Illnesses
Description	New onset chronic illnesses include diabetes, asthma, allergies, autoimmune diseases.
Time Frame	During the extended safety follow-up (ESFU) period (from Day 31 to Month 6)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Extended Safety Follow Up (ESFU) cohort, which included all the subjects for whom the ESFU contact was completed.

Arm/Group Title	Boostrix Group	Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
Measure Participants	1444	718
Count of Participants [Participants]	2 0.1%	3 0.4%

Adverse Events

Time Frame	Solicited local and general symptoms: during the 15-day (Day 0-14) follow-up period after vaccination; Unsolicited AEs: during the 31-day (Day 0-30) follow-up period after vaccination; SAEs: during the entire study period, including the ESFU phase (Month 0 - Month 6).
Arm/Group Title	Boostrix Group		Adacel Group
Arm/Group Description	Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.		Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.
All Cause Mortality
	Boostrix Group		Adacel Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1522 (0.1%)		1/762 (0.1%)
Serious Adverse Events
	Boostrix Group		Adacel Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/1522 (1.4%)		13/762 (1.7%)
Blood and lymphatic system disorders
Anaemia	0/1522 (0%)	0	1/762 (0.1%)	1
Cardiac disorders
Cardiac failure congestive	1/1522 (0.1%)	1	0/762 (0%)	0
Coronary artery stenosis	1/1522 (0.1%)	1	0/762 (0%)	0
Acute myocardial infarction	0/1522 (0%)	0	1/762 (0.1%)	1
Myocardial infarction	0/1522 (0%)	0	1/762 (0.1%)	1
Gastrointestinal disorders
Abdominal pain upper	1/1522 (0.1%)	1	0/762 (0%)	0
Colitis	1/1522 (0.1%)	1	0/762 (0%)	0
Gastritis	0/1522 (0%)	0	1/762 (0.1%)	1
Gastroenteritis	1/1522 (0.1%)	1	0/762 (0%)	0
Pancreatitis	0/1522 (0%)	0	1/762 (0.1%)	1
Peptic ulcer	0/1522 (0%)	0	1/762 (0.1%)	1
Upper gastrointestinal hemorrhage	0/1522 (0%)	0	1/762 (0.1%)	1
Hepatobiliary disorders
Bile duct obstruction	1/1522 (0.1%)	1	0/762 (0%)	0
Cholelithiasis	1/1522 (0.1%)	1	0/762 (0%)	0
Infections and infestations
Diverticulitis	1/1522 (0.1%)	1	0/762 (0%)	0
Herpes oesophagitis	1/1522 (0.1%)	1	0/762 (0%)	0
Localized infection	0/1522 (0%)	0	1/762 (0.1%)	1
Meningitis aseptic	0/1522 (0%)	0	1/762 (0.1%)	1
Injury, poisoning and procedural complications
Thermal burn	0/1522 (0%)	0	1/762 (0.1%)	1
Cervical vertebral fracture	1/1522 (0.1%)	1	0/762 (0%)	0
Patella fracture	1/1522 (0.1%)	1	0/762 (0%)	0
Metabolism and nutrition disorders
Dehydration	3/1522 (0.2%)	3	0/762 (0%)	0
Gout	1/1522 (0.1%)	1	0/762 (0%)	0
Hyponatraemia	1/1522 (0.1%)	1	0/762 (0%)	0
Malnutrition	1/1522 (0.1%)	1	0/762 (0%)	0
Hypokalaemia	1/1522 (0.1%)	1	0/762 (0%)	0
Musculoskeletal and connective tissue disorders
Arthritis	0/1522 (0%)	0	1/762 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	1/1522 (0.1%)	1	0/762 (0%)	0
Prostate cancer	0/1522 (0%)	0	1/762 (0.1%)	1
Ovarian cancer	1/1522 (0.1%)	1	0/762 (0%)	0
Squamous cell carcinoma	0/1522 (0%)	0	1/762 (0.1%)	1
Uterine leiomyoma	1/1522 (0.1%)	1	0/762 (0%)	0
Nervous system disorders
Presyncope	1/1522 (0.1%)	1	0/762 (0%)	0
Cerebrovascular accident	0/1522 (0%)	0	1/762 (0.1%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	2/1522 (0.1%)	2	0/762 (0%)	0
Psychiatric disorders
Schizoaffective disorder	1/1522 (0.1%)	1	0/762 (0%)	0
Renal and urinary disorders
Urge incontinence	0/1522 (0%)	0	1/762 (0.1%)	1
Reproductive system and breast disorders
Menometrorrhagia	2/1522 (0.1%)	2	0/762 (0%)	0
Menorrhagia	0/1522 (0%)	0	1/762 (0.1%)	1
Pelvic pain	1/1522 (0.1%)	1	0/762 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/1522 (0.1%)	1	0/762 (0%)	0
Surgical and medical procedures
Skin graft	0/1522 (0%)	0	1/762 (0.1%)	1
Vascular disorders
Deep vein thrombosis	1/1522 (0.1%)	1	0/762 (0%)	0
Other (Not Including Serious) Adverse Events
	Boostrix Group		Adacel Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1108/1522 (72.8%)		595/762 (78.1%)
Gastrointestinal disorders
Gastrointestinal disorder	235/1522 (15.4%)	235	130/762 (17.1%)	130
General disorders
Fatigue	419/1522 (27.5%)	420	214/762 (28.1%)	214
Pain	905/1522 (59.5%)	917	516/762 (67.7%)	530
Pyrexia	82/1522 (5.4%)	82	60/762 (7.9%)	61
Swelling	261/1522 (17.1%)	261	190/762 (24.9%)	191
Nervous system disorders
Headache	448/1522 (29.4%)	450	230/762 (30.2%)	232
Skin and subcutaneous tissue disorders
Erythema	313/1522 (20.6%)	313	201/762 (26.4%)	201

Limitations/Caveats

[Not Specified]

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.