Concomitant Use of Gardasil (V501) (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) With Combined Diphtheria, Tetanus, Pertussis Vaccine and Meningococcal Conjugate Vaccine in Adolescents - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment
Conditions:	Neoplasms, Glandular and Epithelial Diphtheria Tetanus Whooping Cough Meningitis
Interventions:	Biological: Comparator: Quadrivalent Human Papillomavirus (HPV) vaccine Biological: Comparator: Menactra™ (Concomitant) Biological: Comparator: Adacel™ (Concomitant) Biological: Comparator: Menactra™ (Non-concomitant) Biological: Comparator: Adacel™

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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	Concomitant Administration	Non-concomitant Administration
STARTED	518	524
COMPLETED	499	494
NOT COMPLETED	19	30
Lost to Follow-up	6	14
Withdrawal by Subject	12	14
Protocol Deviation	0	1
Moved	0	1
Patient Discontinued for Other	1	0

	Concomitant Administration	Non-concomitant Administration	Total
Number of Participants [units: participants]	518	524	1042
Age [units: years] Mean ± Standard Deviation	12.5 ± 1.84	12.7 ± 1.90	12.6 ± 1.88
Age, Customized [units: participants]
9 Years of Age and Under	0	0	0
10 to 17 Years of Age	518	524	1042
Over 17 Years of Age	0	0	0
Gender [units: participants]
Female	308	340	648
Male	210	184	394
Race/Ethnicity [units: participants]
Asian	5	7	12
Black	54	74	128
Hispanic American	42	29	71
Indian	1	1	2
Multi-Racial	9	6	15
Native American	1	3	4
White	406	404	810

Outcome Measures

1. Primary:

Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months) [ 7 Months ]

Hide Outcome Measure 1

Measure Type	Primary
Measure Title	Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months)
Measure Description	No text entered.
Time Frame	7 Months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Reporting Groups

	Description
Concomitant Administration	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Non-concomitant Administration	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™

Measured Values

	Concomitant Administration	Non-concomitant Administration
Number of Participants Analyzed [units: participants]	418	418
Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months) [units: Participants]	416	417

Statistical Analysis 1 for Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months)

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Miettinen & Nurminen
P Value ^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -5%
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.

2. Primary:

Number of Subjects Who Seroconverted for HPV Type 11 (HPV 11 ≥ 16 mMU/mL) by Week 4 Postdose 3 (7 Months) [ 7 Months ]

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3. Primary:

Number of Subjects Who Seroconverted for HPV Type 16 (HPV 16 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months) [ 7 Months ]

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4. Primary:

Number of Subjects Who Seroconverted for HPV Type 18 (HPV 18≥ 24 mMU/mL) by Week 4 Postdose 3 (7 Months) [ 7 Months ]

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5. Primary:

Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup A One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [ 7 Months ]

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6. Primary:

Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup C One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [ 7 Months ]

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7. Primary:

Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup W-135 One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [ 7 Months ]

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8. Primary:

Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup Y One Month Postvaccination With Menactra™ [ 7 Months ]

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9. Primary:

Number of Subjects Who Achieved Acceptable Levels of Titers (Diphtheria ≥ 0.1 IU/mL) to Diphtheria One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

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10. Primary:

Number of Subjects Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥ 0.1 IU/mL) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

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11. Primary:

Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [ 7 Months ]

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12. Primary:

Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [ 7 Months ]

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13. Primary:

Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [ 7 Months ]

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14. Primary:

Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [ 7 Months ]

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15. Primary:

Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

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16. Primary:

Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

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17. Primary:

Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

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18. Primary:

Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [ 7 Months ]

Show Outcome Measure 18

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2005_092, V501-025
Study First Received:	May 11, 2006
Results First Received:	May 19, 2009
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00325130 History of Changes
Health Authority:	United States: Food and Drug Administration