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Cervical Intraepithelial Neoplasm (CIN)-Warts Efficacy Trial in Women (Gardasil)(V501-013)(COMPLETED)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00092521
First Posted: September 28, 2004
Last Update Posted: September 25, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
Results First Submitted: August 3, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Genital Warts
Interventions: Biological: V501
Biological: Comparator: Placebo
Biological: Human Papillomavirus (HPV) 16 Monovalent

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study Protocol 013 (NCT00092521) (N =5759 total randomized) was comprised of two sub-studies: Protocol 011 (NCT00517309) (N=1877 total randomized) and Protocol 012 (NCT00092482) (N=3882 total randomized). Final safety data are presented in the results for Protocol 013 (NCT00092521): the final participant visit took place on 19 January 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2 and Month 6) with the Quadrivalent Human papillomavirus (HPV) vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2 and Month 6) with the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 Base Study Monovalent HPV (Type 16) Vaccine was not part of the pre-specified efficacy analysis population.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 were vaccinated (at Day 1, Month 2 and Month 6) with placebo.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension This group includes subjects who entered the extension including subjects who in the base study received fewer than the full three doses of Quadrivalent HPV vaccine during the base study (i.e., subjects who received placebo in the base study; subjects who received monovalent [type 16] HPV vaccine in the base study, or subjects who received <=2 doses of quadrivalent HPV vaccine in the base study). Subjects who discontinued the base portion of the study could enter the extension portion of the study. In the extension period subjects designated as "Completed Period" are those who received three doses of quadrivalent HPV vaccine and completed all required follow-up visits. Subjects designated as "Not Completed" are those who: a) Received all three vaccinations, but did not complete follow-up; b) Did not receive all vaccinations, but completed follow-up, or c) Did not receive all vaccinations, and did not complete follow-up.

Participant Flow for 3 periods

Period 1:   Vaccination (Day 1 Through Month 7)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine   Group 2 - Base Study Monovalent HPV (Type 16) Vaccine   Group 3 - Base Study Placebo   Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension
STARTED   2723   304   2732   0 
COMPLETED   2583   290   2586   0 
NOT COMPLETED   140   14   146   0 
Randomized Not Vaccinated                6                0                7                0 
Adverse Event                1                0                7                0 
Death                0                0                1                0 
Lost to Follow-up                51                6                44                0 
Pregnancy                5                0                7                0 
Withdrawal by Subject                59                7                62                0 
Moved                14                1                18                0 
Unblinded                2                0                0                0 
New Medical History (Not AE)                2                0                0                0 

Period 2:   Follow-Up (After Month 7)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine   Group 2 - Base Study Monovalent HPV (Type 16) Vaccine   Group 3 - Base Study Placebo   Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension
STARTED   2599 [1]   291 [1]   2607 [1]   0 
COMPLETED   2353   155   1959   0 
NOT COMPLETED   246   136   648   0 
Subjects Continuing                34                4                35                0 
Subjects in Extension                13                109                412                0 
Adverse Event                1                0                0                0 
Death                2                0                1                0 
Lost to Follow-up                113                14                108                0 
Protocol Violation                1                1                5                0 
Withdrawal by Subject                40                6                51                0 
Moved                32                2                28                0 
Site Terminated                3                0                3                0 
Travel                2                0                0                0 
Visits Compressed                5                0                5                0 
[1] Includes subjects who did not receive 3 doses of vaccine/placebo but continued into the follow-up

Period 3:   Extension Study (Group 4)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine   Group 2 - Base Study Monovalent HPV (Type 16) Vaccine   Group 3 - Base Study Placebo   Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension
STARTED   0   0   0   844 
Initiated Extension Study   0   0   0   829 
Received >=1 Dose in Extension Study   0   0   0   801 
COMPLETED   0   0   0   635 
NOT COMPLETED   0   0   0   209 
Excluded ineligible for extension                0                0                0                23 
Adverse Event                0                0                0                2 
Lost to Follow-up                0                0                0                87 
Pregnancy                0                0                0                4 
Protocol Violation                0                0                0                2 
Withdrawal by Subject                0                0                0                46 
Moved                0                0                0                16 
Site Terminated                0                0                0                4 
Unable/unwilling to return                0                0                0                25 



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2 and Month 6) with the Quadrivalent HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2 and Month 6) with the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 were vaccinated (at Day 1, Month 2 and Month 6) with placebo.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Total Total of all reporting groups

Baseline Measures
   Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine   Group 2 - Base Study Monovalent HPV (Type 16) Vaccine   Group 3 - Base Study Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 2723   304   2732   5759 
Age 
[Units: Years]
Mean (Standard Deviation)
 20.2  (1.8)   20.2  (1.74)   20.3  (1.8)   20.3  (1.8) 
Age 
[Units: Years]
Median (Full Range)
 20 
 (16 to 24) 
 20 
 (16 to 24) 
 20 
 (16 to 24) 
 20 
 (16 to 24) 
Age, Customized [1] 
[Units: Participants]
       
16 to 24 Years of Age   2723   304   2732   5759 
[1] Although the upper age limit for this study was 23 years old, four subjects aged 24 were randomized into the study.
Gender 
[Units: Participants]
       
Female   2723   304   2732   5759 
Male   0   0   0   0 
Race/Ethnicity, Customized 
[Units: Participants]
       
Asian   151   27   165   343 
Black   136   5   167   308 
Hispanic American   567   93   566   1226 
Native American   10   2   10   22 
White   1600   171   1558   3329 
Other - Unspecified   259   6   266   531 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer   [ Time Frame: Follow-up through end of study (4 years) ]

2.  Primary:   Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]   [ Time Frame: Follow-up through end of study (4 years) ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description Number of subjects at risk included randomized subjects who had follow-up. For Group 4 (Extension), number of subjects at risk included those who received >=1 vaccination in the extension study. Both serious and Other AEs were collected in the base period and only serious AEs were collected in the extension period.

Frequency Threshold
Threshold above which other adverse events are reported   1%  

Reporting Groups
  Description
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2 and Month 6) with the Quadrivalent HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2 and Month 6) with the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 were vaccinated (at Day 1, Month 2 and Month 6) with placebo.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension This group includes subjects who entered the extension including subjects who in the base study received fewer than the full three doses of Quadrivalent HPV vaccine during the base study (i.e., subjects who received placebo in the base study; subjects who received monovalent [type 16] HPV vaccine in the base study, or subjects who received <=2 doses of quadrivalent HPV vaccine in the base study). Subjects who discontinued the base portion of the study could enter the extension portion of the study. In the extension period subjects designated as "Completed Period" are those who received three doses of quadrivalent HPV vaccine and completed all required follow-up visits. Subjects designated as "Not Completed" are those who: a) Received all three vaccinations, but did not complete follow-up; b) Did not receive all vaccinations, but completed follow-up, or c) Did not receive all vaccinations, and did not complete follow-up.

Other Adverse Events
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine   Group 2 - Base Study Monovalent HPV (Type 16) Vaccine   Group 3 - Base Study Placebo   Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension
Total, Other (not including serious) Adverse Events         
# participants affected / at risk   2458/2673 (91.96%)   276/299 (92.31%)   2331/2672 (87.24%)   0/0 
Gastrointestinal disorders         
Abdominal pain * 1         
# participants affected / at risk   88/2673 (3.29%)   8/299 (2.68%)   81/2672 (3.03%)   0/0 
Abdominal pain upper * 1         
# participants affected / at risk   82/2673 (3.07%)   5/299 (1.67%)   87/2672 (3.26%)   0/0 
Diarrhea * 1         
# participants affected / at risk   105/2673 (3.93%)   9/299 (3.01%)   96/2672 (3.59%)   0/0 
Dyspepsia * 1         
# participants affected / at risk   17/2673 (0.64%)   5/299 (1.67%)   16/2672 (0.60%)   0/0 
Gastritis * 1         
# participants affected / at risk   22/2673 (0.82%)   4/299 (1.34%)   13/2672 (0.49%)   0/0 
Nausea * 1         
# participants affected / at risk   210/2673 (7.86%)   23/299 (7.69%)   174/2672 (6.51%)   0/0 
Toothache * 1         
# participants affected / at risk   48/2673 (1.80%)   4/299 (1.34%)   40/2672 (1.50%)   0/0 
Vomiting * 1         
# participants affected / at risk   62/2673 (2.32%)   9/299 (3.01%)   56/2672 (2.10%)   0/0 
General disorders         
Asthenia * 1         
# participants affected / at risk   29/2673 (1.08%)   7/299 (2.34%)   25/2672 (0.94%)   0/0 
Fatigue * 1         
# participants affected / at risk   73/2673 (2.73%)   12/299 (4.01%)   102/2672 (3.82%)   0/0 
Malaise * 1         
# participants affected / at risk   47/2673 (1.76%)   3/299 (1.00%)   40/2672 (1.50%)   0/0 
Pain * 1         
# participants affected / at risk   19/2673 (0.71%)   3/299 (1.00%)   26/2672 (0.97%)   0/0 
Pyrexia * 1         
# participants affected / at risk   436/2673 (16.31%)   33/299 (11.04%)   348/2672 (13.02%)   0/0 
Injection site erythema † 1         
# participants affected / at risk   659/2673 (24.65%)   84/299 (28.09%)   450/2672 (16.84%)   0/0 
Injection site haematoma † 1         
# participants affected / at risk   94/2673 (3.52%)   6/299 (2.01%)   97/2672 (3.63%)   0/0 
Injection site hypersensitivity † 1         
# participants affected / at risk   27/2673 (1.01%)   9/299 (3.01%)   22/2672 (0.82%)   0/0 
Injection site pain † 1         
# participants affected / at risk   2281/2673 (85.33%)   242/299 (80.94%)   2014/2672 (75.37%)   0/0 
Injection site pruritus † 1         
# participants affected / at risk   109/2673 (4.08%)   12/299 (4.01%)   80/2672 (2.99%)   0/0 
Injection site reaction † 1         
# participants affected / at risk   22/2673 (0.82%)   4/299 (1.34%)   17/2672 (0.64%)   0/0 
Injection site swelling † 1         
# participants affected / at risk   694/2673 (25.96%)   70/299 (23.41%)   413/2672 (15.46%)   0/0 
Infections and infestations         
Gastroenteritis * 1         
# participants affected / at risk   17/2673 (0.64%)   3/299 (1.00%)   18/2672 (0.67%)   0/0 
Influenza * 1         
# participants affected / at risk   124/2673 (4.64%)   18/299 (6.02%)   113/2672 (4.23%)   0/0 
Nasopharyngitis * 1         
# participants affected / at risk   185/2673 (6.92%)   22/299 (7.36%)   166/2672 (6.21%)   0/0 
Pharyngitis * 1         
# participants affected / at risk   32/2673 (1.20%)   3/299 (1.00%)   31/2672 (1.16%)   0/0 
Sinusitis * 1         
# participants affected / at risk   22/2673 (0.82%)   3/299 (1.00%)   18/2672 (0.67%)   0/0 
Tonsillitis * 1         
# participants affected / at risk   26/2673 (0.97%)   2/299 (0.67%)   29/2672 (1.09%)   0/0 
Upper respiratory tract infection * 1         
# participants affected / at risk   36/2673 (1.35%)   9/299 (3.01%)   42/2672 (1.57%)   0/0 
Vulvovaginal candidiasis * 1         
# participants affected / at risk   10/2673 (0.37%)   4/299 (1.34%)   16/2672 (0.60%)   0/0 
Injury, poisoning and procedural complications         
Procedural pain * 1         
# participants affected / at risk   4/2673 (0.15%)   3/299 (1.00%)   4/2672 (0.15%)   0/0 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1         
# participants affected / at risk   27/2673 (1.01%)   0/299 (0.00%)   25/2672 (0.94%)   0/0 
Back Pain * 1         
# participants affected / at risk   68/2673 (2.54%)   10/299 (3.34%)   63/2672 (2.36%)   0/0 
Muscle Spasms * 1         
# participants affected / at risk   14/2673 (0.52%)   3/299 (1.00%)   12/2672 (0.45%)   0/0 
Myalgia * 1         
# participants affected / at risk   49/2673 (1.83%)   6/299 (2.01%)   54/2672 (2.02%)   0/0 
Pain in Extremity * 1         
# participants affected / at risk   55/2673 (2.06%)   7/299 (2.34%)   57/2672 (2.13%)   0/0 
Nervous system disorders         
Dizziness * 1         
# participants affected / at risk   123/2673 (4.60%)   18/299 (6.02%)   114/2672 (4.27%)   0/0 
Headache * 1         
# participants affected / at risk   802/2673 (30.00%)   103/299 (34.45%)   76/2672 (2.84%)   0/0 
Migraine * 1         
# participants affected / at risk   23/2673 (0.86%)   3/299 (1.00%)   15/2672 (0.56%)   0/0 
Somnolence * 1         
# participants affected / at risk   30/2673 (1.12%)   0/299 (0.00%)   32/2672 (1.20%)   0/0 
Psychiatric disorders         
Insomnia * 1         
# participants affected / at risk   35/2673 (1.31%)   2/299 (0.67%)   23/2672 (0.86%)   0/0 
Reproductive system and breast disorders         
Dysmenorrhea * 1         
# participants affected / at risk   106/2673 (3.97%)   11/299 (3.68%)   100/2672 (3.74%)   0/0 
Pelvic Pain * 1         
# participants affected / at risk   14/2673 (0.52%)   4/299 (1.34%)   22/2672 (0.82%)   0/0 
Respiratory, thoracic and mediastinal disorders         
Cough * 1         
# participants affected / at risk   59/2673 (2.21%)   6/299 (2.01%)   40/2672 (1.50%)   0/0 
Nasal congestion * 1         
# participants affected / at risk   26/2673 (0.97%)   3/299 (1.00%)   15/2672 (0.56%)   0/0 
Oropharyngeal pain * 1         
# participants affected / at risk   109/2673 (4.08%)   14/299 (4.68%)   116/2672 (4.34%)   0/0 
Skin and subcutaneous tissue disorders         
Dermatitis allergic * 1         
# participants affected / at risk   5/2673 (0.19%)   3/299 (1.00%)   10/2672 (0.37%)   0/0 
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 11.1



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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