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Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001)

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ClinicalTrials.gov Identifier: NCT00543543
Recruitment Status : Completed
First Posted : October 15, 2007
Results First Posted : December 19, 2014
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Cervical Cancer
Vulvar Cancer
Vaginal Cancer
Genital Warts
Human Papillomavirus Infection
Interventions Biological: Comparator: GARDASIL
Biological: Experimental: V503
Enrollment 14840

Recruitment Details  
Pre-assignment Details A total of 15,334 participants were screened and 14,840 were randomized into the study.
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description V503 (9-Valent Human Papillomavirus [HPV] Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study. V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study. V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study. Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Period Title: Base Study
Started 315 7106 310 7109
Completed 3 Vaccinations 300 6928 297 6934
Completed 295 [1] 5854 [2] 296 [1] 5887 [2]
Not Completed 20 1252 14 1222
Reason Not Completed
Adverse Event             1             11             0             5
Lost to Follow-up             12             749             9             701
Physician Decision             0             4             0             7
Protocol Violation             0             6             0             6
Withdrawal by Subject             7             482             5             503
[1]
Follow-up was up to 7 months
[2]
Follow-up was up to 54 months
Period Title: Extension Study
Started 0 [1] 150 [2] 0 [1] 3050 [3]
Completed 0 150 0 2824
Not Completed 0 0 0 226
Reason Not Completed
Adverse Event             0             0             0             5
Lost to Follow-up             0             0             0             77
Physician Decision             0             0             0             7
Pregnancy             0             0             0             6
Protocol Violation             0             0             0             11
Withdrawal by Subject             0             0             0             120
[1]
This group did not participate in the Extension Study
[2]
Cohort 1
[3]
Cohort 2
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil Total
Hide Arm/Group Description V503 (9-Valent Human Papillomavirus [HPV] Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study. V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study. V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study. Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study. Total of all reporting groups
Overall Number of Baseline Participants 315 7106 310 7109 14840
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 315 participants 7106 participants 310 participants 7109 participants 14840 participants
21.7  (2.4) 21.9  (2.5) 21.9  (2.4) 21.8  (2.5) 21.9  (2.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 315 participants 7106 participants 310 participants 7109 participants 14840 participants
Female
315
 100.0%
7106
 100.0%
310
 100.0%
7109
 100.0%
14840
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)
Hide Description HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports data based on the protocol-specified plan of conducting hypothesis testing when at least 30 cases had accumulated. The cutoff date for this analysis was 10 April 2013. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Time Frame From Day 1 until >=30 cases accumulate, up to Month 54 in the base study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Efficacy population included all participants who received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable day ranges, were seronegative at Day 1 and PCR negative at Day 1 through Day 7 to the relevant HPV types, and had at least 1 follow-up visit following Month 7.
Arm/Group Title Mid-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 6016 6017
Measure Type: Number
Unit of Measure: Cases per 10,000 person-years follow-up
0.5 15.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact test, 1-sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 96.7
Confidence Interval (2-Sided) 95%
80.9 to 99.8
Estimation Comments Vaccine efficacy = 100 * [1 - (incidence rate with V503 / incidence rate with Gardasil)]. The pre-specified success criterion was a lower bound of the 95% confidence interval of observed efficacy of >25%.
2.Primary Outcome
Title Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)
Hide Description HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports cumulative study data through 10 March 2014. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Time Frame Up to Month 54 in the base study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Efficacy population included all participants who received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable day ranges, were seronegative at Day 1 and PCR negative at Day 1 through Day 7 to the relevant HPV types, and had at least 1 follow-up visit following Month 7.
Arm/Group Title Mid-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 6016 6017
Measure Type: Number
Unit of Measure: Cases per 10,000 person-years follow-up
0.5 19.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact test, 1-sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 97.4
Confidence Interval (2-Sided) 95%
85.0 to 99.9
Estimation Comments Vaccine efficacy = 100 * [1 - (incidence rate with V503 / incidence rate with Gardasil)]. The pre-specified success criterion was a lower bound of the 95% confidence interval of observed efficacy of >25%.
3.Primary Outcome
Title Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58
Hide Description Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. Statistical analysis was performed only for HPV types contained in both vaccines.
Time Frame 4 weeks postdose 3 in the base study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Immunogenicity population included all participants who were not protocol violators, received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable ranges, were seronegative at Day 1 and PCR negative from Day 1- Month 7 for the relevant HPV types, and had a Month 7 serum sample collected within an acceptable range
Arm/Group Title Mid-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 6792 6795
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck U/mL
Anti-HPV Type 6 (n=3993, 3975)
893.1
(871.7 to 915.1)
875.2
(854.2 to 896.8)
Anti-HPV Type 11 (n=3995, 3982)
666.3
(649.6 to 683.4)
830.0
(809.2 to 851.4)
Anti-HPV Type 16 (n=4032, 4062)
3131.1
(3057.1 to 3206.9)
3156.6
(3082.3 to 3232.7)
Anti-HPV Type 18 (n=4539, 4541)
804.6
(782.7 to 827.1)
678.7
(660.2 to 697.7)
Anti-HPV Type 31 (n=4466, 4377)
658.4
(636.7 to 680.9)
9.7
(9.4 to 10.1)
Anti-HPV Type 33 (n=4702, 4691)
415.9
(405.6 to 426.4)
NA [1] 
(NA to NA)
Anti-HPV Type 45 (n=4792, 4750)
252.8
(246.2 to 259.6)
NA [2] 
(NA to NA)
Anti-HPV Type 52 (n=4455, 4335)
379.7
(371.6 to 388.0)
NA [2] 
(NA to NA)
Anti-HPV Type 58 (n=4486, 4446)
482.5
(469.9 to 495.3)
NA [1] 
(NA to NA)
[1]
The GMT value was <4 milli Merck U/mL
[2]
The GMT value was <3 milli Merck U/mL
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments Anti-HPV Type 6
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority required that the lower bound of the two-sided confidence interval (CI) of the GMT ratio was >0.67
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.99 to 1.06
Estimation Comments GMT ratio = GMT (V503) / GMT (Gardasil)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments Anti-HPV Type 11
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority required that the lower bound of the two-sided CI of the GMT ratio was >0.67
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.77 to 0.83
Estimation Comments GMT ratio = GMT (V503) / GMT (Gardasil)
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments Anti-HPV Type 16
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority required that the lower bound of the two-sided CI of the GMT ratio was >0.67
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.96 to 1.03
Estimation Comments GMT ratio = GMT (V503) / GMT (Gardasil)
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments Anti-HPV Type 18
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority required that the lower bound of the two-sided CI of the GMT ratio was >0.67
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
1.14 to 1.23
Estimation Comments GMT ratio = GMT (V503) / GMT (Gardasil)
4.Primary Outcome
Title Base Study: Percentage of Participants With One or More Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Time Frame Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received >=1 vaccination and had safety follow-up
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 310 7071 305 7078
Measure Type: Number
Unit of Measure: Percentage of participants
92.6 94.2 92.8 91.1
5.Primary Outcome
Title Base Study: Percentage of Participants With One or More Injection-site Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Time Frame Up to Day 5 after any vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received >=1 vaccination and had safety follow-up
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 310 7071 305 7078
Measure Type: Number
Unit of Measure: Percentage of participants
87.7 90.7 90.5 84.9
6.Primary Outcome
Title Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs.
Time Frame Up to Day 15 after any vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received >=1 vaccination and had safety follow-up
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 310 7071 305 7078
Measure Type: Number
Unit of Measure: Percentage of participants
53.5 55.8 51.1 54.9
7.Primary Outcome
Title Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. An AE that is judged by the investigator to be “definitely related,” “probably related,” or “possibly related” to the study drug is defined as a vaccine-related AE.
Time Frame Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received >=1 vaccination and had safety follow-up
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 310 7071 305 7078
Measure Type: Number
Unit of Measure: Percentage of participants
90.0 92.2 92.8 87.6
8.Primary Outcome
Title Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
Hide Description An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event.
Time Frame Up to Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received >=1 vaccination and had safety follow-up
Arm/Group Title Low-dose V503 Mid-dose V503 High-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 310 7071 305 7078
Measure Type: Number
Unit of Measure: Percentage of participants
0.6 0.1 0.0 0.1
9.Secondary Outcome
Title Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection
Hide Description Combined Incidence of HPV Type 31/33/45/52/58-related persistent infection as determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. Persistent infection was defined as infection detected in samples from >=2 consecutive visits 6 months (+/-1 month visit window) or longer apart. Incidence was defined as the number of cases of persistent infection per 10,000 person-years of follow-up in a treatment arm.
Time Frame Up to Month 54 in the base study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Efficacy population included all participants who received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable day ranges, were seronegative at Day 1 and PCR negative at Day 1 through Day 7 to the relevant HPV types, and had at least 1 follow-up visit following Month 7.
Arm/Group Title Mid-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 5941 5955
Measure Type: Number
Unit of Measure: Cases per 10,000 person-years follow-up
21.5 538.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mid-dose V503, Gardasil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 96.0
Confidence Interval (2-Sided) 95%
94.6 to 97.1
Estimation Comments Vaccine efficacy = 100 * [1 - (incidence rate with V503 / incidence rate with Gardasil)]. The pre-specified success criterion was a lower bound of the 95% confidence interval of observed efficacy of >25%.
10.Secondary Outcome
Title Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58
Hide Description Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Types 33, 45, 52, and 58: ≥8.
Time Frame 4 weeks postdose 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per-protocol Immunogenicity population included all participants who were not protocol violators, received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable ranges, were seronegative at Day 1 and PCR negative from Day 1 - Month 7 for the relevant HPV types, and had a Month 7 serum sample collected within an acceptable range
Arm/Group Title Mid-dose V503 Gardasil
Hide Arm/Group Description:
V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.
Overall Number of Participants Analyzed 6792 6795
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Anti-HPV Type 6 (n=3993, 3975)
99.8
(99.6 to 99.9)
99.8
(99.7 to 99.9)
Anti-HPV Type 11 (n=3995, 3982)
100
(99.9 to 100)
99.9
(99.8 to 100)
Anti-HPV Type 16 (n=4032, 4062)
100
(99.9 to 100)
100
(99.8 to 100)
Anti-HPV Type 18 (n=4539, 4541)
99.8
(99.7 to 99.9)
99.7
(99.5 to 99.8)
Anti-HPV Type 31 (n=4466, 4377)
99.8
(99.6 to 99.9)
50.1
(48.7 to 51.6)
Anti-HPV Type 33 (n=4702, 4691)
99.7
(99.5 to 99.9)
12.7
(11.8 to 13.7)
Anti-HPV Type 45 (n=4792, 4750)
99.6
(99.4 to 99.8)
9.2
(8.4 to 10.0)
Anti-HPV Type 52 (n=4455, 4335)
99.8
(99.6 to 99.9)
2.6
(2.2 to 3.1)
Anti-HPV Type 58 (n=4486, 4446)
99.8
(99.6 to 99.9)
20.4
(19.2 to 21.6)
11.Other Pre-specified Outcome
Title Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Predose 4
Hide Description Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. This outcome measure applied to Cohort 1 participants only.
Time Frame Month 60: predose 4 in the Extension Study (Cohort 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 1 who received all 3 vaccinations of mid-dose V503 in the Base Study, were seronegative at Day 1 and PCR negative from Day 1 to Month 7 for the relevant HPV types, had no other violation that could interfere with evaluation of immune response, and provided post-dose 4 serum.
Arm/Group Title Extension Study: Mid-dose V503 (Cohort 1)
Hide Arm/Group Description:
V503 mid-dose 0.5 mL injection in a 3-dose regimen in the Base Study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Overall Number of Participants Analyzed 150
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck U/mL
Anti-HPV Type 6 (n=101)
143.1
(117.9 to 173.7)
Anti-HPV Type 11 (n=112)
82.9
(68.1 to 100.9)
Anti-HPV Type 16 (n=128)
324.4
(266.7 to 394.7)
Anti-HPV Type 18 (n=142)
62.5
(49.5 to 78.9)
Anti-HPV Type 31 (n=135)
69.2
(56.6 to 84.4)
Anti-HPV Type 33 (n=141)
44.7
(37.0 to 54.1)
Anti-HPV Type 45 (n=148)
20.8
(17.0 to 25.5)
Anti-HPV Type 52 (n=134)
33.7
(27.6 to 41.1)
Anti-HPV Type 58 (n=132)
50.9
(40.9 to 63.3)
12.Other Pre-specified Outcome
Title Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 7 Postdose 4
Hide Description Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. This outcome measure applied to Cohort 1 participants only.
Time Frame Month 60 + 1 week: Day 7 postdose 4 in the Extension Study (Cohort 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 1 who received all 3 vaccinations of mid-dose V503 in the Base Study, were seronegative at Day 1 and PCR negative from Day 1 to Month 7 for the relevant HPV types, had no other violation that could interfere with evaluation of immune response, and provided post-dose 4 serum.
Arm/Group Title Extension Study: Mid-dose V503 (Cohort 1)
Hide Arm/Group Description:
V503 mid-dose 0.5 mL injection in a 3-dose regimen in the Base Study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Overall Number of Participants Analyzed 150
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck U/mL
Anti-HPV Type 6 (n=109)
2180.5
(1826.2 to 2603.7)
Anti-HPV Type 11 (n=109)
2228.7
(1852.5 to 2681.3)
Anti-HPV Type 16 (n=126)
7986.3
(6795.7 to 9385.6)
Anti-HPV Type 18 (n=138)
2399.0
(2049.4 to 2808.1)
Anti-HPV Type 31 (n=131)
1462.2
(1263.9 to 1691.5)
Anti-HPV Type 33 (n=137)
1709.0
(1466.7 to 1991.2)
Anti-HPV Type 45 (n=144)
323.0
(277.2 to 376.5)
Anti-HPV Type 52 (n=131)
1078.1
(907.2 to 1281.2)
Anti-HPV Type 58 (n=129)
1801.8
(1530.5 to 2121.2)
13.Other Pre-specified Outcome
Title Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 28 Postdose 4
Hide Description Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. This outcome measure applied to Cohort 1 participants only.
Time Frame Month 61: 28 days postdose 4 in the Extension Study (Cohort 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in Cohort 1 who received all 3 vaccinations of mid-dose V503 in the Base Study, were seronegative at Day 1 and PCR negative from Day 1 to Month 7 for the relevant HPV types, had no other violation that could interfere with evaluation of immune response, and provided post-dose 4 serum.
Arm/Group Title Extension Study: Mid-dose V503 (Cohort 1)
Hide Arm/Group Description:
V503 mid-dose 0.5 mL injection in a 3-dose regimen in the Base Study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
Overall Number of Participants Analyzed 150
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck U/mL
Anti-HPV Type 6 (n=109)
2585.0
(2239.5 to 2983.8)
Anti-HPV Type 11 (n=109)
2548.7
(2191.4 to 2964.3)
Anti-HPV Type 16 (n=123)
10904.3
(9605.6 to 12378.7)
Anti-HPV Type 18 (n=137)
2907.9
(2531.1 to 3340.7)
Anti-HPV Type 31 (n=130)
1745.4
(1538.8 to 1979.8)
Anti-HPV Type 33 (n=136)
2094.9
(1848.7 to 2373.9)
Anti-HPV Type 45 (n=143)
440.0
(386.9 to 500.4)
Anti-HPV Type 52 (n=129)
1131.5
(991.6 to 1291.1)
Anti-HPV Type 58 (n=127)
2024.6
(1803.1 to 2273.2)
Time Frame Base Study: SAEs up to Month (M) 7 (low- and high-dose V503) or up to M54 (mid-dose V503 and Gardasil); non-serious AEs up to Day 15 after vaccination. Cohort 1: SAEs M60 to 61; non-serious AEs up to Day 15 after vaccination 4. Cohort 2: SAEs M60 to 67.
Adverse Event Reporting Description The analysis population included all participants who received >=1 vaccination and had safety follow-up. Non-serious AEs were not solicited in Extension Cohort 2; however, some non-serious AEs were voluntarily reported.
 
Arm/Group Title Base Study: Low-Dose V503 Base Study: Mid-dose V503 Base Study: High-dose V503 Base Study: Gardasil Extension Study: Mid-dose V503 (Cohort 1) Extension Study: Mid-dose V503 (Cohort 2)
Hide Arm/Group Description V503 (9-Valent HPV Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study. V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) will receive a fourth V503 mid-dose vaccination in the extension study. V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study. Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) will be offered the V503 mid-dose 3-dose regimen in the extension study. V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL fourth dose administration in Base Study participants who were randomized to receive a 3-dose regimen of V503 (9-Valent HPV) mid-dose 0.5 mL (Cohort 1). V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL 3-dose regimen administration on Base Study participants who were randomized to receive a 3-dose regimen of Gardasil (4-Valent HPV Vaccine) (Cohort 2).
All-Cause Mortality
Base Study: Low-Dose V503 Base Study: Mid-dose V503 Base Study: High-dose V503 Base Study: Gardasil Extension Study: Mid-dose V503 (Cohort 1) Extension Study: Mid-dose V503 (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Base Study: Low-Dose V503 Base Study: Mid-dose V503 Base Study: High-dose V503 Base Study: Gardasil Extension Study: Mid-dose V503 (Cohort 1) Extension Study: Mid-dose V503 (Cohort 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/310 (1.29%)      233/7071 (3.30%)      5/305 (1.64%)      184/7078 (2.60%)      1/150 (0.67%)      25/3049 (0.82%)    
Blood and lymphatic system disorders             
Anaemia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cardiac disorders             
Aortic valve incompetence  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Postural orthostatic tachycardia syndrome  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Atrial fibrillation  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Congenital, familial and genetic disorders             
Cleft lip and palate  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Diverticulitis Meckel's  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ear and labyrinth disorders             
Vertigo positional  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Abdominal pain lower  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Anal fistula  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Coeliac disease  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Colitis ulcerative  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Crohn's disease  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Diarrhoea  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Enterocolitis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Gastritis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Haemorrhoids  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Inguinal hernia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Irritable bowel syndrome  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Omental infarction  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pancreatitis acute  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
General disorders             
Accidental death  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Non-cardiac chest pain  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pyrexia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Sudden death  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hepatobiliary disorders             
Cholangitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cholecystitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cholelithiasis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cholestasis of pregnancy  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Immune system disorders             
Allergy to vaccine  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Anaphylactic reaction  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hypersensitivity  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Sarcoidosis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Infections and infestations             
Abscess jaw  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Appendicitis  1  1/310 (0.32%)  1 9/7071 (0.13%)  9 0/305 (0.00%)  0 16/7078 (0.23%)  16 0/150 (0.00%)  0 2/3049 (0.07%)  2
Bronchitis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cellulitis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cholecystitis infective  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Chronic tonsillitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Conjunctivitis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Dengue fever  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Enteritis infectious  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Gastroenteritis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Gastroenteritis viral  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Haemorrhagic fever  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Infectious mononucleosis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Influenza  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pelvic inflammatory disease  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pharyngitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Post abortion infection  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pyelonephritis  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pyelonephritis acute  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Septic shock  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Tonsillitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Tonsillitis streptococcal  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Urinary tract infection  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 1/305 (0.33%)  1 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Urosepsis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Viral pharyngitis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Wound infection  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pneumonia  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  2
Postoperative wound infection  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 1/150 (0.67%)  1 0/3049 (0.00%)  0
Injury, poisoning and procedural complications             
Bladder injury  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Burns second degree  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Craniocerebral injury  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Femur fracture  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Foreign body in eye  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Fracture displacement  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hand fracture  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Head injury  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Humerus fracture  1  0/310 (0.00%)  0 1/7071 (0.01%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Joint dislocation  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ligament rupture  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Lower limb fracture  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Multiple injuries  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Neck injury  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Poisoning  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Post procedural haemorrhage  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pubis fracture  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Road traffic accident  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Spinal compression fracture  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Spinal cord injury  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Spinal cord injury cervical  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ulna fracture  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Metabolism and nutrition disorders             
Hyperglycaemia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Fibromyalgia  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Myalgia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Osteoarthritis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Acute lymphocytic leukaemia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Acute promyelocytic leukaemia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Adenocarcinoma gastric  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Adenocarcinoma of the cervix  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Brain neoplasm  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ependymoma  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Leukaemic infiltration brain  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Malignant melanoma  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Malignant melanoma in situ  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Malignant palate neoplasm  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Nasal cavity cancer  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ovarian neoplasm  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pituitary tumour benign  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Respiratory papilloma  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Thyroid cancer  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Breast cancer  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Glioma  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Nervous system disorders             
Benign intracranial hypertension  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cerebral haemorrhage  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Diabetic coma  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Epilepsy  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Facial paresis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Headache  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hydrocephalus  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hypersomnia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hypoaesthesia  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Intracranial venous sinus thrombosis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Migraine  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Multiple sclerosis  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 1/3049 (0.03%)  1
Neuritis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Orthostatic intolerance  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Presyncope  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Sciatica  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Sensory disturbance  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Spondylitic myelopathy  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Syncope  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Tension headache  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Trigeminal nerve disorder  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Pregnancy, puerperium and perinatal conditions             
Abortion spontaneous  1  1/310 (0.32%)  1 36/7071 (0.51%)  38 1/305 (0.33%)  1 26/7078 (0.37%)  28 0/150 (0.00%)  0 8/3049 (0.26%)  8
Abortion spontaneous complete  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Abortion spontaneous incomplete  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Blighted ovum  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cephalo-pelvic disproportion  1  0/310 (0.00%)  0 4/7071 (0.06%)  4 0/305 (0.00%)  0 6/7078 (0.08%)  6 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cervix dystocia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ectopic pregnancy  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
False labour  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Foetal death  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 1/305 (0.33%)  1 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Foetal distress syndrome  1  1/310 (0.32%)  1 4/7071 (0.06%)  4 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Foetal malposition  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Foetal malpresentation  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Gestational diabetes  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 1/3049 (0.03%)  1
Labour complication  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Oligohydramnios  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pre-eclampsia  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 1/305 (0.33%)  1 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Premature labour  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Premature rupture of membranes  1  0/310 (0.00%)  0 4/7071 (0.06%)  4 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Prolonged labour  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Uterine contractions during pregnancy  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Psychiatric disorders             
Anorexia and bulimia syndrome  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Anorexia nervosa  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Bipolar disorder  1  0/310 (0.00%)  0 3/7071 (0.04%)  3 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Completed suicide  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Depression  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Major depression  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Renal and urinary disorders             
Calculus ureteric  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Calculus urinary  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cystitis haemorrhagic  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Nephrolithiasis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Renal failure  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Renal failure acute  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Renal colic  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Reproductive system and breast disorders             
Bartholinitis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cervical dysplasia  1  0/310 (0.00%)  0 5/7071 (0.07%)  5 0/305 (0.00%)  0 3/7078 (0.04%)  3 0/150 (0.00%)  0 0/3049 (0.00%)  0
Cervix haemorrhage uterine  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Dysmenorrhoea  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Endometriosis  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Fallopian tube cyst  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Ovarian cyst  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 2/7078 (0.03%)  2 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pelvic pain  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Asthmatic crisis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Dyspnoea  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Nasal polyps  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pneumonia aspiration  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Pneumothorax  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Respiratory failure  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Vocal cord polyp  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Skin and subcutaneous tissue disorders             
Urticaria  2  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 1/3049 (0.03%)  1
Surgical and medical procedures             
Abortion induced  1  1/310 (0.32%)  1 73/7071 (1.03%)  76 2/305 (0.66%)  2 53/7078 (0.75%)  53 0/150 (0.00%)  0 3/3049 (0.10%)  3
Vascular disorders             
Axillary vein thrombosis  1  0/310 (0.00%)  0 0/7071 (0.00%)  0 0/305 (0.00%)  0 1/7078 (0.01%)  1 0/150 (0.00%)  0 0/3049 (0.00%)  0
Deep vein thrombosis  1  0/310 (0.00%)  0 1/7071 (0.01%)  1 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Hypovolaemic shock  1  0/310 (0.00%)  0 2/7071 (0.03%)  2 0/305 (0.00%)  0 0/7078 (0.00%)  0 0/150 (0.00%)  0 0/3049 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
2
Term from vocabulary, MedDRA version 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Base Study: Low-Dose V503 Base Study: Mid-dose V503 Base Study: High-dose V503 Base Study: Gardasil Extension Study: Mid-dose V503 (Cohort 1) Extension Study: Mid-dose V503 (Cohort 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   278/310 (89.68%)      6551/7071 (92.65%)      280/305 (91.80%)      6268/7078 (88.56%)      130/150 (86.67%)      89/3049 (2.92%)    
Gastrointestinal disorders             
Nausea  1  22/310 (7.10%)  23 513/7071 (7.25%)  617 18/305 (5.90%)  20 459/7078 (6.48%)  551 2/150 (1.33%)  2 4/3049 (0.13%)  4
General disorders             
Injection site erythema  1  100/310 (32.26%)  157 2411/7071 (34.10%)  3597 91/305 (29.84%)  140 1810/7078 (25.57%)  2564 33/150 (22.00%)  34 9/3049 (0.30%)  9
Injection site pain  1  267/310 (86.13%)  684 6360/7071 (89.94%)  15383 273/305 (89.51%)  672 5911/7078 (83.51%)  13001 124/150 (82.67%)  128 59/3049 (1.94%)  94
Injection site pruritus  1  18/310 (5.81%)  21 389/7071 (5.50%)  494 14/305 (4.59%)  16 282/7078 (3.98%)  341 1/150 (0.67%)  1 1/3049 (0.03%)  1
Injection site swelling  1  100/310 (32.26%)  154 2836/7071 (40.11%)  4527 103/305 (33.77%)  168 2035/7078 (28.75%)  2988 49/150 (32.67%)  51 12/3049 (0.39%)  12
Pyrexia  1  30/310 (9.68%)  35 469/7071 (6.63%)  563 17/305 (5.57%)  19 463/7078 (6.54%)  550 6/150 (4.00%)  6 7/3049 (0.23%)  7
Infections and infestations             
Influenza  1  20/310 (6.45%)  22 312/7071 (4.41%)  343 12/305 (3.93%)  12 296/7078 (4.18%)  314 4/150 (2.67%)  5 5/3049 (0.16%)  5
Nasopharyngitis  1  10/310 (3.23%)  11 376/7071 (5.32%)  412 12/305 (3.93%)  13 389/7078 (5.50%)  420 1/150 (0.67%)  1 0/3049 (0.00%)  0
Nervous system disorders             
Dizziness  1  17/310 (5.48%)  20 346/7071 (4.89%)  405 11/305 (3.61%)  13 307/7078 (4.34%)  368 0/150 (0.00%)  0 2/3049 (0.07%)  2
Headache  1  65/310 (20.97%)  100 1879/7071 (26.57%)  3071 66/305 (21.64%)  106 1756/7078 (24.81%)  2788 32/150 (21.33%)  41 11/3049 (0.36%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Publications of Results:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00543543     History of Changes
Other Study ID Numbers: V503-001
2007_538
First Submitted: October 12, 2007
First Posted: October 15, 2007
Results First Submitted: December 12, 2014
Results First Posted: December 19, 2014
Last Update Posted: November 27, 2018