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    Clinical Trial Results:
    A phase III, double-blind, randomized, controlled study to evaluate the safety, immunogenicity and efficacy of GlaxoSmithKline Biologicals’ HPV 16/18 L1/AS04 vaccine administered intramuscularly according to a three-dose schedule (0, 1, 6 month) in healthy adult female subjects aged 26 years and above.

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2005-002546-20
    Trial protocol
    		 GB   PT  
    Global end of trial date
    29 Jan 2014

    Results information
    Results version number
    		 v2
    This version publication date
    27 Apr 2016
    First version publication date
    15 Jul 2015
    Other versions
    		 v1 (removed from public view) , v3
    Version creation reason
    • New data added to full data set
    • Correction of full data set
    Data for secondary endpoints have been added. Data correction due to a system error in EudraCT – Results.

    Trial information

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    Trial identification
    Sponsor protocol code
    104820
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00294047
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    19 Dec 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jan 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    -To demonstrate efficacy of the candidate vaccine in the prevention of (1) persistent infection (6-month definition) with HPV-16 or HPV-18 (by polymerase chain reaction [PCR]) and/or (2) histopathologically confirmed CIN1+ associated with HPV-16 or HPV-18 cervical infection detected within the lesional component of the cervical tissue specimen (by PCR) (combined endpoint), overall and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus (by enzyme-linked immunosorbent assay [ELISA]). If efficacy is demonstrated, the following objective will be assessed sequentially: -To demonstrate efficacy of the candidate vaccine in the prevention of (1) persistent infection (6-month definition) with HPV-16 or HPV-18 (by PCR) and/or (2) histopathologically-confirmed CIN1+ associated with HPV-16 or HPV-18 cervical infection detected using the HPV TAA, overall and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus (by ELISA).
    Protection of trial subjects
    As with all injectable vaccines, appropriate medical treatment was always readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccinee remained under medical supervision for 30 minutes after vaccination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Feb 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Ethical reason, Safety, Regulatory reason, Scientific research
    Long term follow-up duration
    		 84 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 195
    Country: Number of subjects enrolled
    Canada: 422
    Country: Number of subjects enrolled
    Mexico: 1298
    Country: Number of subjects enrolled
    Netherlands: 361
    Country: Number of subjects enrolled
    Peru: 178
    Country: Number of subjects enrolled
    Philippines: 738
    Country: Number of subjects enrolled
    Portugal: 212
    Country: Number of subjects enrolled
    Russian Federation: 300
    Country: Number of subjects enrolled
    Singapore: 234
    Country: Number of subjects enrolled
    Thailand: 500
    Country: Number of subjects enrolled
    United Kingdom: 272
    Country: Number of subjects enrolled
    United States: 1072
    Worldwide total number of subjects
    5782
    EEA total number of subjects
    845
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    5782
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Some subjects completed the study at Month 36 since they did not want to participate to the one-year extension up to Month 48. The number of subjects who participated up to Month 48 in the Cervarix Group = 2305 (80.0%) and in the Aluminium Hydroxide Group = 2281 (79.4%).

    Pre-assignment
    Screening details
    		 Enrolment was stratified by (1) age, with the majority of subjects in age strata 26 – 35 years and 36 – 45 years (about 45% each) and about 10% in the age stratum 46+ years, and (2) previous HPV history (in each age stratum, the number of women with a history of HPV infection/treatment was limited to approximately 15%).

    Pre-assignment period milestones
    Number of subjects started
    		 5782
    Number of subjects completed
    		 5752

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 No vaccination received: 30
    Period 1
    Period 1 title
    Month 48 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cervarix Group
    Arm description
    		 Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

    Arm title
    		 Aluminium Hydroxide Group
    Arm description
    		 Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
    Arm type
    		 Placebo Comparator

    Investigational medicinal product name
    Placebo control
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were planned to receive three doses of the control vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

    Number of subjects in period 1 [1]
    		Cervarix Group Aluminium Hydroxide Group
    Started
    2881
    2871
    Completed
    2456
    2438
    Not completed
    425
    433
         Consent withdrawn by subject
    111
    115
         Adverse event, non-fatal
    28
    13
         Unspecified
    10
    14
         Lost to follow-up
    272
    287
         Protocol deviation
    4
    4
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the 5782 subjects enrolled in the study, not all received the study vaccination, hence only 5752 started.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cervarix Group
    Reporting group description
    		 Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Reporting group title
    Aluminium Hydroxide Group
    Reporting group description
    		 Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Reporting group values
    		 Cervarix Group Aluminium Hydroxide Group Total
    Number of subjects
    		 2881 2871 5752
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 37 ( 7.24 ) 37 ( 7.32 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2881 2871 5752
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Cervarix Group
    Reporting group description
    		 Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Reporting group title
    Aluminium Hydroxide Group
    Reporting group description
    		 Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Primary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection.

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection. [1]
    End point description
    CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus
    End point type
    Primary
    End point timeframe
    Up to Month 48
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N= 1898;1854)
    7
    36
        HPV-16, DNA- and sero- subjects (N=1545;1521)
    5
    27
        HPV-18, DNA- and sero- subjects (N=1597;1571)
    2
    10
        HPV-16/18, DNA- and sero+ subjects (N=900;864)
    2
    14
        HPV-16, DNA- and sero+ subjects (N=605;594)
    1
    9
        HPV-18, DNA- and sero+ subjects (N=574;550)
    1
    5
        HPV-16/18, overall (N=2224;2190)
    9
    51
        HPV-16, overall (N=2167;2131)
    6
    36
        HPV-18, overall (N=2203;2165)
    3
    16
    No statistical analyses for this end point

    Primary: Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA). [2]
    End point description
    CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Primary
    End point timeframe
    Up to Month 48
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1898;1854)
    7
    36
        HPV-16, DNA- and sero- subjects (N=1545;1521)
    5
    27
        HPV-18, DNA- and sero- subjects (N=1597;1571)
    2
    10
        HPV-16/18, DNA- and sero+ subjects (N=900;864)
    2
    12
        HPV-16, DNA- and sero+ subjects (N=605;594)
    1
    8
        HPV-18, DNA- and sero+ subjects (N=574;550)
    1
    4
        HPV-16/18, overall (N=2224;2190)
    9
    49
        HPV-16, overall (N=2167;2131)
    6
    35
        HPV-18, overall (N=2203;2165)
    3
    15
    No statistical analyses for this end point

    Primary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN) 1+ associated with HPV-16 and/or -18 cervical infection.

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN) 1+ associated with HPV-16 and/or -18 cervical infection. [3]
    End point description
    CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
    End point type
    Primary
    End point timeframe
    Up to Month 84
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2168
    2147
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N= 1852;1818)
    7
    71
        HPV-16, DNA- and sero- subjects (N=1507;1491)
    5
    53
        HPV-18, DNA- and sero- subjects (N=1565;1541)
    3
    20
        HPV-16/18, DNA- and sero+ subjects (N=870;849)
    3
    16
        HPV-16, DNA- and sero+ subjects (N=588;584)
    2
    10
        HPV-18, DNA- and sero+ subjects (N=552;540)
    1
    6
        HPV-16/18, overall (N=2168;2147)
    10
    90
        HPV-16, overall (N=2112;2091)
    7
    63
        HPV-18, overall (N=2149;2123)
    4
    29
    No statistical analyses for this end point

    Primary: Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA). [4]
    End point description
    CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Primary
    End point timeframe
    Up to Month 84
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: he analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2168
    2147
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1852;1818)
    7
    71
        HPV-16, DNA- and sero- subjects (N=1507;1491)
    5
    53
        HPV-18, DNA- and sero- subjects (N=1565;1541)
    2
    20
        HPV-16/18, DNA- and sero+ subjects (N=870;849)
    3
    14
        HPV-16, DNA- and sero+ subjects (N=588;584)
    2
    9
        HPV-18, DNA- and sero+ subjects (N=552;540)
    1
    5
        HPV-16/18, overall (N=2168;2147)
    10
    88
        HPV-16, overall (N=2112;2091)
    7
    62
        HPV-18, overall (N=2149;2123)
    3
    28
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done in: - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2178
    2152
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1859;1822)
    6
    34
        HPV-16, DNA- and sero- subjects (N=1518;1495)
    5
    26
        HPV-18, DNA- and sero- subjects (N=1566;1542)
    1
    8
        HPV-16/18, DNA- and sero+ subjects (N=880;851)
    2
    11
        HPV-16, DNA- and sero+ subjects (N=591;583)
    1
    8
        HPV-18, DNA- and sero+ subjects (N=562;543)
    1
    3
        HPV-16/18, overall (N=2178;2152)
    8
    45
        HPV-16, overall (N=2126;2094)
    6
    34
        HPV-18, overall (N=2160;2127)
    2
    11
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (12-month definition) with human papillomavirus (HPV)-16 or HPV-18

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    End point title
    		 Number of subjects with persistent infection (12-month definition) with human papillomavirus (HPV)-16 or HPV-18
    End point description
    Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2146
    2124
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1832;1800)
    2
    18
        HPV-16, DNA- and sero- subjects (N=1499;1476)
    1
    12
        HPV-18, DNA- and sero- subjects (N=1543;1525)
    1
    6
        HPV-16/18, DNA- and sero+ subjects (N=864;839)
    0
    3
        HPV-16, DNA- and sero+ subjects (N=579;577)
    0
    2
        HPV-18, DNA- and sero+ subjects (N=553;532)
    0
    1
        HPV-16/18, overall (N=2146;2124)
    2
    21
        HPV-16, overall (N=2095;2069)
    1
    14
        HPV-18, overall (N=2128;2099)
    1
    7
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month Definition) with oncogenic HPV types individually or in combinations.

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    End point title
    		 Number of subjects with persistent infection (6-month Definition) with oncogenic HPV types individually or in combinations.
    End point description
    Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2179
    2154
    Units: Subjects
        HPV-16 (N=2126;2094)
    6
    34
        HPV-18 (N=2160;2127)
    2
    11
        HPV-31 (N=2126;2132)
    4
    19
        HPV-33 (N=2158;2136)
    8
    6
        HPV-35 (N=2165;2144)
    8
    13
        HPV-39 (N=2150;2119)
    20
    11
        HPV-45 (N=2160;2130)
    4
    17
        HPV-51 (N=2125;2113)
    27
    26
        HPV-52 (N=2113;2101)
    33
    38
        HPV-56 (N=2154;2123)
    16
    20
        HPV-58 (N=2152;2135)
    12
    8
        HPV-59 (N=2158;2126)
    12
    11
        HPV-66 (N=2141;2122)
    27
    27
        HPV-68 (N=2138;2128)
    15
    23
        HPV-31/45 (N=2175;2152)
    8
    35
        HPV-31/45/33/52/58 (N=2179;2154)
    58
    83
        HPV-39/45/59/68 (N=2179;2154)
    50
    60
        HPV-31/33/35/52/58 (N=2179;2154)
    63
    80
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2179;2154)
    132
    146
        HPV-HRW (N=2179;2154)
    163
    185
        HPV-HR (N=2179;2154)
    170
    217
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (12-month Definition) with oncogenic HPV types individually or in combinations.

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    End point title
    		 Number of subjects with persistent infection (12-month Definition) with oncogenic HPV types individually or in combinations.
    End point description
    Persistent HPV infection (12-month definition) = detection of the same HPV type(s) by PCR in cervical samples at available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2147
    2126
    Units: Subjects
        HPV-16 (N=2095;2069)
    1
    14
        HPV-18 (N=2128;2099)
    1
    7
        HPV-31 (N=2096;2104)
    2
    10
        HPV-33 (N=2126;2110)
    5
    5
        HPV-35 (N=2133;2116)
    3
    8
        HPV-39 (N=2119;2091)
    12
    5
        HPV-45 (N=2129;2102)
    4
    8
        HPV-51 (N=2093;2086)
    11
    14
        HPV-52 (N=2081;2074)
    21
    23
        HPV-56 (N=2124;2096)
    4
    8
        HPV-58 (N=2120;2108)
    8
    7
        HPV-59 (N=2126;2098)
    4
    3
        HPV-66 (N=2109;2094)
    10
    8
        HPV-68 (N=2106;2100)
    7
    13
        HPV-31/45 (N=2144;2124)
    6
    17
        HPV-31/45/33/52/58 (N=2147;2126)
    39
    49
        HPV-39/45/59/68 (N=2147;2126)
    27
    29
        HPV-31/33/35/52/58 (N=2147;2126)
    38
    51
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2147;2126)
    70
    84
        HPV-HRW (N=2147;2126)
    86
    105
        HPV-HR (N=2147;2126)
    88
    122
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen
    End point description
    CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Note: Results for seropositive status were not analysed.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1898;1854)
    0
    4
        HPV-16, DNA- and sero- subjects (N=1545;1521)
    0
    3
        HPV-18, DNA- and sero- subjects (N=1597;1571)
    0
    2
        HPV-16/18, overall (N=2224;2190)
    0
    6
        HPV-16, overall (N=2167;2131)
    0
    3
        HPV-18, overall (N=2203;2165)
    0
    4
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1898;1854)
    1
    7
        HPV-16, DNA- and sero- subjects (N=1545;1521)
    0
    5
        HPV-18, DNA- and sero- subjects (N=1597;1571)
    1
    3
        HPV-16/18, DNA- and sero+ subjects (N=900;864)
    0
    3
        HPV-16, DNA- and sero+ subjects (N=605;594)
    0
    1
        HPV-18, DNA- and sero+ subjects (N=574;550)
    0
    2
        HPV-16/18, overall (N=2224;2190)
    1
    11
        HPV-16, overall (N=2167;2131)
    0
    6
        HPV-18, overall (N=2203;2165)
    1
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2740
    2737
    Units: Subjects
        HPV-16/18
    35
    56
        HPV-16
    24
    42
        HPV-18
    13
    20
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ irrespective of HPV cervical infection and irrespective of baseline HPV DNA status

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ irrespective of HPV cervical infection and irrespective of baseline HPV DNA status
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2740
    2737
    Units: Subjects
        CIN1+
    152
    178
    No statistical analyses for this end point

    Secondary: Number of subjects with any cytological abnormalities associated with HPV-16 or HPV-18 cervical infection

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    End point title
    		 Number of subjects with any cytological abnormalities associated with HPV-16 or HPV-18 cervical infection
    End point description
    Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Results for seropositive status were not analysed.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1898;1854)
    2
    31
        HPV-16, DNA- and sero- subjects (N=1545;1521)
    2
    24
        HPV-18, DNA- and sero- subjects (N=1597;1571)
    0
    8
        HPV-16/18, overall (N=2224;2190)
    5
    38
        HPV-16 (N=2167;2131)
    4
    27
        HPV-18 (N=2203;2165)
    1
    12
    No statistical analyses for this end point

    Secondary: Number of subjects with cytological abnormalities associated with oncogenic HPV types individually or in combinations

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    End point title
    		 Number of subjects with cytological abnormalities associated with oncogenic HPV types individually or in combinations
    End point description
    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2225
    2192
    Units: Subjects
        HPV-16 (N=2167;2131)
    4
    27
        HPV-18 (N=2203;2165)
    1
    12
        HPV-31 (N=2172;2170)
    4
    12
        HPV-33 (N=2204;2173)
    4
    4
        HPV-35 (N=2211;2181)
    4
    10
        HPV-39 (N=2196;2156)
    10
    11
        HPV-45 (N=2206;2168)
    3
    17
        HPV-51 (N=2171;2149)
    21
    18
        HPV-52 (N=2158;2139)
    19
    19
        HPV-56 (N=2200;2158)
    9
    19
        HPV-58 (N=2198;2172)
    12
    6
        HPV-59 (N=2202;2164)
    4
    15
        HPV-66 (N=2187;2160)
    13
    26
        HPV-68 (N=2184;2164)
    8
    8
        HPV-31/45 (N=2221;2190)
    7
    28
        HPV-31/45/33/52/58 (N=2225;2192)
    40
    54
        HPV-39/45/59/68 (N=2225;2192)
    24
    48
        HPV-31/33/35/52/58 (N=2225;2192)
    41
    49
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2225;2192)
    79
    107
        HPV-HRW (N=2225;2192)
    94
    126
        HPV-HR (N=2225;2192)
    96
    148
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically confirmed reduction of local cervical therapy

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    End point title
    		 Number of subjects with histopathologically confirmed reduction of local cervical therapy
    End point description
    Detection was done on all subjects irrespective of their baseline HPV DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2740
    2737
    Units: Subjects
        Reduction of local cervical therapy
    76
    84
    No statistical analyses for this end point

    Secondary: Number of subjects with first colposcopy

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    End point title
    		 Number of subjects with first colposcopy
    End point description
    Detection was done on all subjects irrespective of their baseline HPV DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2741
    2738
    Units: Subjects
        First colposcopy
    392
    422
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2772
    2779
    Units: Subjects
        HPV-16/18
    90
    158
        HPV-16
    64
    118
        HPV-18
    30
    52
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-confirmed CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-confirmed CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types)
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2772
    2779
    Units: Subjects
        HPV-16/18
    89
    155
        HPV-16
    63
    117
        HPV-18
    29
    49
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects against HPV-16 in the immunogenicity subset.

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    End point title
    		 Number of seroconverted subjects against HPV-16 in the immunogenicity subset.
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-16 assay cut-off value was defined as greater than or equal to 8 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    406
    374
    Units: Subjects
        Sero- before vaccination (N=406;374)
    0
    0
        Sero- at Month 7 (N=406;371)
    406
    13
        Sero- at Month 12 (N=384;349)
    384
    28
        Sero- at Month 18 (N=377;340)
    377
    9
        Sero- at Month 24 (N=392;350)
    392
    11
        Sero- at Month 36 (N=361;320)
    361
    23
        Sero- at Month 48 (N=345;316)
    345
    31
        Sero+ before vaccination (N=170;179)
    170
    179
        Sero+ at Month 7 (N=170;179)
    170
    166
        Sero+ at Month 12 (N=154;158)
    154
    151
        Sero+ at Month 18 (N=147;154)
    147
    136
        Sero+ at Month 24 (N=158;165)
    158
    144
        Sero+ at Month 36 (N=137;146)
    137
    131
        Sero+ at Month 48 (N=132;145)
    132
    135
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects against HPV-18 in the immunogenicity subset.

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    End point title
    		 Number of seroconverted subjects against HPV-18 in the immunogenicity subset.
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-18 assay cut-off value was defined as greater than or equal to 7 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    405
    379
    Units: Subjects
        Sero- before vaccination (N=405;379)
    0
    0
        Sero- at Month 7 (N=405;374)
    405
    12
        Sero- at Month 12 (N=376;352)
    375
    16
        Sero- at Month 18 (N=366;347)
    366
    12
        Sero- at Month 24 (N=389;358)
    387
    14
        Sero- at Month 36 (N=348;328)
    346
    14
        Sero- at Month 48 (N=338;320)
    336
    16
        Sero+ before vaccination (N=163;164)
    163
    164
        Sero+ at Month 7 (N=163;161)
    163
    146
        Sero+ at Month 12 (N=154;144)
    154
    133
        Sero+ at Month 18 (N=149;141)
    149
    118
        Sero+ at Month 24 (N=153;150)
    153
    114
        Sero+ at Month 36 (N=142;131)
    142
    92
        sero+ at Month 48 (N=133;131)
    133
    94
    No statistical analyses for this end point

    Secondary: Geometric mean concentrations (GMCs) against HPV-16 antibody in the immunogenicity subset.

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    End point title
    		 Geometric mean concentrations (GMCs) against HPV-16 antibody in the immunogenicity subset.
    End point description
    GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    406
    374
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Sero-before vaccination (N=406;374)
    0 (0 to 0)
    0 (0 to 0)
        Sero- at Month 7 (N=406;371)
    5412.9 (4934.3 to 5938)
    4.3 (4.1 to 4.4)
        Sero- at Month 12 (N=384;349)
    1542.5 (1393.2 to 1707.8)
    4.4 (4.2 to 4.5)
        Sero- at Month 18 (N=377;340)
    992.6 (893.9 to 1102.2)
    4.1 (4 to 4.2)
        Sero- at Month 24 (N=392;350)
    827.8 (745.2 to 919.5)
    4.2 (4.1 to 4.4)
        Sero- at Month 36 (N=361;320)
    612.9 (550.1 to 682.8)
    4.5 (4.2 to 4.7)
        Sero- at Month 48 (N=345;316)
    546.2 (490.4 to 608.2)
    4.6 (4.4 to 4.9)
        Sero+ before vaccination (N=170;179)
    39.3 (33.6 to 45.9)
    38.6 (33.2 to 44.9)
        Sero+ at Month 7 (N=170;179)
    5845.5 (5113.8 to 6682)
    33.4 (28.2 to 39.5)
        Sero+ at month 12 (N=154;158)
    2705.8 (2313.2 to 3165.1)
    38 (32 to 45.3)
        Sero+ at Month 18 (N=147;154)
    2104.7 (1780.5 to 2487.8)
    30.5 (25.2 to 36.9)
        Sero+ at Month 24 (N=158;165)
    1883.5 (1599.4 to 2218.1)
    29.6 (24.5 to 35.7)
        Sero+ at month 36 (N=137;146)
    1363.8 (1138.2 to 1634.2)
    30.6 (25.3 to 37)
        Sero+ at Month 48 (N=132;145)
    1261.2 (1048.4 to 1517.1)
    34.3 (28.8 to 40.8)
    No statistical analyses for this end point

    Secondary: Geometric mean concentrations (GMCs) against HPV-18 antibody in the immunogenicity subset.

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    End point title
    		 Geometric mean concentrations (GMCs) against HPV-18 antibody in the immunogenicity subset.
    End point description
    GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    405
    379
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Sero- before vaccination (N=405;379)
    0 (0 to 0)
    0 (0 to 0)
        Sero- at Month 7 (N=405;374)
    2567.7 (2339.5 to 2818.2)
    3.7 (3.6 to 3.9)
        Sero- at Month 12 (N=376;352)
    645.3 (576.6 to 722.1)
    3.7 (3.6 to 3.9)
        Sero- at Month 18 (N=366;347)
    402.6 (359.7 to 450.6)
    3.7 (3.6 to 3.8)
        Sero- at Month 24 (N=389;358)
    321.7 (286.9 to 360.7)
    3.7 (3.6 to 3.9)
        Sero- at Month 36 (N=348;328)
    245.9 (218.5 to 276.8)
    3.7 (3.6 to 3.8)
        Sero- at Month 48 (N=338;320)
    228.5 (201.9 to 258.7)
    3.7 (3.6 to 3.8)
        Sero+ before vaccination (N=163;164)
    23 (19.9 to 26.7)
    24.2 (20.6 to 28.4)
        Sero+ at Month 7 (N=163;161)
    2933.9 (2557.1 to 3366.3)
    21.9 (18.1 to 26.5)
        Sero+ at Month 12 (N=154;144)
    936.2 (796.4 to 1100.4)
    23.6 (19.4 to 28.7)
        Sero+ at Month 18 (N=149;141)
    661.3 (560.9 to 779.7)
    19.5 (15.7 to 24.2)
        Sero+ at Month 24 (N=153;150)
    573.6 (487.7 to 674.6)
    16.6 (13.5 to 20.5)
        Sero+ at Month 36 (N=142;131)
    423.1 (357.9 to 500.1)
    16.4 (12.9 to 20.7)
        Sero+ at Month 48 (N=133;131)
    392.3 (328.9 to 468)
    15.9 (12.7 to 19.9)
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects against HPV-16 and HPV-18 viral neutralization in a selected subset of subjects.

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    End point title
    		 Number of seroconverted subjects against HPV-16 and HPV-18 viral neutralization in a selected subset of subjects.
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-16/18 assay cut-off value was defined as greater than or equal to 40 Estimated dose 50% (ED50). Sero- subjects are subjects who had an antibody concentration below 40 ED50 prior to vaccination. Sero+ subjects are subjects who had an antibody concentration equal to or above 50 ED50 prior to vaccination. ED50 = the estimated serum dilution reducing the signal generated by viral infection by 50%.
    End point type
    Secondary
    End point timeframe
    Prior to vaccination and at Month 7, 12, 18, 24, 48 and 84.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    38
    37
    Units: Subjects
        HPV-16 sero- [pre-vaccination] (N=37;37)
    0
    0
        HPV-16 sero- [at Month 7] (N=37;37)
    37
    1
        HPV-16 sero- [at Month 12] (N=37;37)
    37
    0
        HPV-16 sero- [at Month 18] (N=36;37)
    36
    0
        HPV-16 sero- [at Month 24] (N=35;37)
    35
    2
        HPV-16 sero- [at Month 48] (N=27;33)
    27
    1
        HPV-16 sero+ [pre-vaccination] (N=4;1)
    4
    1
        HPV-16 sero+ [at Month 7] (N=4;1)
    4
    1
        HPV-16 sero+ [at Month 12] (N=4;1)
    4
    1
        HPV-16 sero+ [at Month 18] (N=4;1)
    4
    1
        HPV-16 sero+ [at Month 24] (N=4;1)
    4
    0
        HPV-16 sero+ [at Month 48] (N=3;1)
    3
    0
        HPV-18 sero- [pre-vaccination] (N=38;35)
    0
    0
        HPV-18 sero- [at Month 7] (N=38;35)
    38
    0
        HPV-18 sero- [at Month 12] (N=38;35)
    38
    0
        HPV-18 sero- [at Month 18] (N=37;35)
    37
    0
        HPV-18 sero- [at Month 24] (N=36;35)
    36
    1
        HPV-18 sero- [at Month 48] (N=29;32)
    29
    0
        HPV-18 sero+ [pre-vaccination] (N=3;3)
    3
    3
        HPV-18 sero+ [at Month 7] (N=3;3)
    3
    2
        HPV-18 sero+ [at Month 12] (N=3;3)
    3
    2
        HPV-18 sero+ [at Month 18] (N=3;3)
    3
    2
        HPV-18 sero+ [at Month 24] (N=3;3)
    3
    2
        HPV-18 sero+ [at Month 48] (N=1;2)
    1
    1
        HPV-16 sero- [at Month 84] (N=20;25)
    19
    1
        HPV-16 sero+ [at Month 84] (N=3;1)
    3
    1
        HPV-18 sero- [at Month 84] (N=22;25)
    22
    0
        HPV-18 sero+ [at Month 84] (N=1;1)
    1
    1
    No statistical analyses for this end point

    Secondary: Geometric mean titers (GMTs) against HPV-16 and HPV-18 viral neutralization antibodies in a selected subset of subjects.

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    End point title
    		 Geometric mean titers (GMTs) against HPV-16 and HPV-18 viral neutralization antibodies in a selected subset of subjects.
    End point description
    Titers are expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects are subjects who had an antibody titer below 40 ED50 prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody titer equal to or above 40 ED50 prior to vaccination. ED50 = Estimated dose 50%, the estimated serum dilution reducing the signal generated by viral infection by 50%.
    End point type
    Secondary
    End point timeframe
    Prior to vaccination and at Month 7, 12, 18, 24, 48 and 84.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    38
    37
    Units: Titers
    geometric mean (confidence interval 95%)
        HPV-16 sero- [pre-vaccination] (N=37;37)
    20 (20 to 20)
    20 (20 to 20)
        HPV-16 sero- [at Month 7] (N=37;37)
    11663.5 (7507.2 to 18120.8)
    20.8 (19.2 to 22.4)
        HPV-16 sero- [at Month 12] (N=37;37)
    5597.7 (3688.3 to 8495.6)
    20 (20 to 20)
        HPV-16 sero- [at Month 18] (N=36;37)
    2175.2 (1390.8 to 3401.9)
    20 (20 to 20)
        HPV-16 sero- [at Month 24] (N=35;37)
    1941.7 (1193 to 3160.4)
    22.3 (18.6 to 26.6)
        HPV-16 sero- [at Month 48] (N=27;33)
    828.9 (488.4 to 1406.7)
    21.4 (18.7 to 24.5)
        HPV-16 sero+ [pre-vaccination] (N=4;1)
    139.3 (32.7 to 594.2)
    45 (45 to 45)
        HPV-16 sero+ [at Month 7] (N=4;1)
    20283.2 (2428.3 to 169422)
    107 (107 to 107)
        HPV-16 sero+ [at Month 12] (N=4;1)
    19484.3 (7049.3 to 53854.2)
    99 (99 to 99)
        HPV-16 sero+ [at Month 18] (N=4;1)
    4393.3 (798.4 to 24175)
    93 (93 to 93)
        HPV-16 sero+ [at Month 24] (N=4;1)
    9459.1 (2168.4 to 41263.7)
    20 (20 to 20)
        HPV-16 sero+ [at Month 48] (N=3;1)
    4187.2 (676.4 to 25921.6)
    20 (20 to 20)
        HPV-18 sero- [pre-vaccination] (N=38;35)
    20 (20 to 20)
    20 (20 to 20)
        HPV-18 sero- [at Month 7] (N=38;35)
    7959.6 (4648 to 13630.7)
    20 (20 to 20)
        HPV-18 sero- [at Month 12] (N=38;35)
    1979.9 (1201.6 to 3262.5)
    20 (20 to 20)
        HPV-18 sero- [at Month 18] (N=37;35)
    1334.6 (793.3 to 2245.3)
    20 (20 to 20)
        HPV-18 sero- [at Month 24] (N=36;35)
    826.6 (493.6 to 1384.1)
    21.4 (18.7 to 24.5)
        HPV-18 sero- [at Month 48] (N=29;32)
    386.1 (203.9 to 731.1)
    20 (20 to 20)
        HPV-18 sero+ [pre-vaccination] (N=3;3)
    84.7 (9.2 to 782.4)
    115.5 (21.5 to 621)
        HPV-18 sero+ [at Month 7] (N=3;3)
    3014.5 (446.3 to 20361.5)
    163.4 (0.8 to 31959.2)
        HPV-18 sero+ [at Month 12] (N=3;3)
    3377.8 (2563.9 to 4450.1)
    167.3 (0.8 to 35164.4)
        HPV-18 sero+ [at Month 18] (N=3;3)
    3125.8 (595.8 to 16398.4)
    254.9 (0.4 to 172814)
        HPV-18 sero+ [at Month 24] (N=3;3)
    2493 (261.2 to 23793.7)
    154.9 (0.4 to 53341.9)
        HPV-18 sero+ [at Month 48] (N=1;2)
    545 (545 to 545)
    86 (0 to 9999)
        HPV-16 sero- [at Month 84] (N=20;25)
    1213.4 (529.8 to 2779.1)
    22.9 (17.3 to 30.4)
        HPV-16 sero+ [at Month 84] (N=3;1)
    5837 (963.7 to 35354.6)
    104 (104 to 104)
        HPV-18 sero- [at Month 84] (N=22;25)
    491.2 (232.9 to 1036)
    20 (20 to 20)
        HPV-18 sero+ [at Month 84] (N=1;1)
    532 (532 to 532)
    968 (968 to 968)
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and Grade 3 solicited local symptoms.

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    End point title
    		 Number of subjects reporting any and Grade 3 solicited local symptoms.
    End point description
    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) after vaccination
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2830
    2831
    Units: Subjects
        Any pain
    2411
    1862
        Grade 3 pain
    303
    73
        Any redness
    1058
    530
        Grade 3 redness
    44
    5
        Any swelling
    1080
    428
        Grade 3 swelling
    97
    11
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any, Grade 3 and related solicited general symptoms.

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    End point title
    		 Number of subjects reporting any, Grade 3 and related solicited general symptoms.
    End point description
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = axillary temperature above 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = axillary temperature above 39.0°C.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) after vaccination
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2832
    2832
    Units: Subjects
        Any arthralgia
    580
    439
        Grade3 arthralgia
    30
    24
        Related arthralgia
    323
    225
        Any fatigue
    1116
    916
        Grade 3 fatigue
    78
    53
        Related fatigue
    678
    545
        Any fever
    308
    248
        Grade 3 fever
    17
    8
        Related fever
    181
    159
        Any gastrointestinal
    664
    592
        Grade 3 gastrointestinal
    60
    54
        Related gastrointestinal
    335
    312
        Any headache
    1165
    1074
        Grade 3 headache
    76
    72
        Related headache
    666
    598
        Any myalgia
    878
    622
        Grade 3 myalgia
    46
    32
        Related myalgia
    541
    391
        Any rash
    185
    124
        Grade 3 rash
    1
    7
        Related rash
    88
    61
        Any urticaria
    258
    201
        Grade 3 urticaria
    21
    18
        Related urticaria
    84
    79
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any, Grade 3 and related unsolicited adverse events (AEs).

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    End point title
    		 Number of subjects reporting any, Grade 3 and related unsolicited adverse events (AEs).
    End point description
    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Grade 3 unsolicited AE = an event that prevented normal activity. A related AE = event assessed by the investigator as causally related to the study vaccination.
    End point type
    Secondary
    End point timeframe
    Within 30 days (Days 0 – 29) post-vaccination period.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2881
    2871
    Units: Subjects
        Any AEs
    1154
    1164
        Grade 3 AEs
    207
    184
        Related AEs
    246
    192
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and related serious adverse events (SAEs).

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    End point title
    		 Number of subjects reporting any and related serious adverse events (SAEs).
    End point description
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. A related SAE was defined as an event assessed by the investigator as causally related to the study vaccination.
    End point type
    Secondary
    End point timeframe
    Up to Month 48 and up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2881
    2871
    Units: Subjects
        Any SAEs, M48
    286
    266
        Related SAEs, M48
    5
    8
        Any SAEs, M84
    291
    269
        Related SAEs, M84
    5
    8
    No statistical analyses for this end point

    Secondary: Number of subjects reporting new onset of chronic disease (NOCDs).

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    End point title
    		 Number of subjects reporting new onset of chronic disease (NOCDs).
    End point description
    NOCDs include autoimmune disorders, asthma and type I diabetes.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2881
    2871
    Units: Subjects
        NOCDs
    143
    165
    No statistical analyses for this end point

    Secondary: Number of subjects reporting new onset of autoimmune disease (NOADs).

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    End point title
    		 Number of subjects reporting new onset of autoimmune disease (NOADs).
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2881
    2871
    Units: Subjects
        NOADs
    24
    24
    No statistical analyses for this end point

    Secondary: Number of subjects reporting medically significant conditions (MAEs).

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    End point title
    		 Number of subjects reporting medically significant conditions (MAEs).
    End point description
    Medically significant conditions were defined as: AEs prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2881
    2871
    Units: Subjects
        MAEs
    1170
    1140
    No statistical analyses for this end point

    Secondary: Number of subjects with pregnancies and their outcomes.

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    End point title
    		 Number of subjects with pregnancies and their outcomes.
    End point description
    Pregnancy outcomes are live infant, premature live infant, elective termination, ectopic pregnancy, spontaneous abortion, lost to follow-up and pregnancy ongoing. For each category it was specified if the infant presents congenital anomaly (CA) or no apparent congenital anomaly (No ACA).
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    359
    357
    Units: Subjects
        Live infant No ACA, M48
    259
    249
        Live infant CA, M48
    4
    7
        Elective termination No ACA, M48
    19
    24
        Elective termination CA, M48
    1
    0
        Ectopic pregnancy, M48
    5
    6
        Spontaneous abortion No ACA, M48
    69
    66
        Spontaneous abortion CA, M48
    0
    1
        Stillbirth No ACA, M48
    0
    2
        Lost to follow-up, M48
    2
    2
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected using the type assignment algorithm (TAA)

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected using the type assignment algorithm (TAA)
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. TAA: Type assignment algorithm. The lesion was assigned to an HPV type found in the lesion if a) the same HPV type was found in at least one of the two (closest) preceding cytology samples, or b) none of the HPV types found in the lesion were found in any of the two preceding cytology samples (isolate HPV types)
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2224
    2190
    Units: Subjects
        HPV-16/18 DNA- (N=2224;2190)
    1
    9
        HPV-16 DNA- (N=2167;2131)
    0
    5
        HPV-18 DNA- (N=2203;2165)
    1
    5
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18.

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18.
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done in: - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2124
    2109
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1815;1786)
    6
    67
        HPV-16, DNA- and sero- subjects (N=1482;1466)
    5
    51
        HPV-18, DNA- and sero- subjects (N=1535;1511)
    1
    17
        HPV-16/18, DNA- and sero+ subjects (N=851;837)
    3
    13
        HPV-16, DNA- and sero+ subjects (N=574;573)
    2
    9
        HPV-18, DNA- and sero+ subjects (N=541;534)
    1
    4
        HPV-16/18, overall (N=2124;2109)
    9
    82
        HPV-16, overall (N=2073;2055)
    7
    60
        HPV-18, overall (N=2108;2085)
    2
    23
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (12-month definition) with human papillomavirus (HPV)-16 or HPV-18.

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    End point title
    		 Number of subjects with persistent infection (12-month definition) with human papillomavirus (HPV)-16 or HPV-18.
    End point description
    Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2093
    2081
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1789;1764)
    2
    37
        HPV-16, DNA- and sero- subjects (N=1464;1447)
    1
    27
        HPV-18, DNA- and sero- subjects (N=1513;1494)
    1
    10
        HPV-16/18, DNA- and sero+ subjects (N=835;825)
    0
    5
        HPV-16, DNA- and sero+ subjects (N=562;567)
    0
    3
        HPV-18, DNA- and sero+ subjects (N=532;523)
    0
    2
        HPV-16/18, overall (N=2093;2081)
    2
    43
        HPV-16, overall (N=2043;2030)
    1
    30
        HPV-18, overall (N=2077;2057)
    1
    13
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month Definition) with oncogenic HPV types individually or in combinations.

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    End point title
    		 Number of subjects with persistent infection (6-month Definition) with oncogenic HPV types individually or in combinations.
    End point description
    Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2125
    2111
    Units: Subjects
        HPV-16 (N=2073;2055)
    7
    60
        HPV-18 (N=2108;2085)
    2
    23
        HPV-31 (N=2073;2090)
    10
    29
        HPV-33 (N=2105;2094)
    12
    9
        HPV-35 (N=2112;2101)
    11
    17
        HPV-39 (N=2097;2078)
    34
    26
        HPV-45 (N=2106;2088)
    9
    30
        HPV-51 (N=2071;2072)
    48
    42
        HPV-52 (N=2060;2058)
    54
    56
        HPV-56 (N=2100;2081)
    28
    30
        HPV-58 (N=2098;2092)
    24
    19
        HPV-59 (N=2105;2083)
    22
    21
        HPV-66 (N=2089;2080)
    45
    49
        HPV-68 (N=2084;2085)
    31
    33
        HPV-31/45 (N=2121;2109)
    19
    57
        HPV-31/45/33/52/58 (N=2125;2111)
    98
    128
        HPV-39/45/59/68 (N=2125;2111)
    92
    102
        HPV-31/33/35/52/58 (N=2125;2111)
    101
    118
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2125;2111)
    206
    220
        HPV-HRW (N=2125;2111)
    255
    274
        HPV-HR (N=2125;2111)
    262
    330
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (12-month Definition) with oncogenic HPV types individually or in combinations.

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    End point title
    		 Number of subjects with persistent infection (12-month Definition) with oncogenic HPV types individually or in combinations.
    End point description
    Persistent HPV infection (12-month definition) = detection of the same HPV type(s) by PCR in cervical samples at available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2094
    2083
    Units: Subjects
        HPV-16 (N=2043;2030)
    1
    30
        HPV-18 (N=2077;2057)
    1
    13
        HPV-31 (N=2044;2062)
    7
    17
        HPV-33 (N=2074;2068)
    9
    7
        HPV-35 (N=2081;2073)
    5
    9
        HPV-39 (N=2067;2050)
    20
    10
        HPV-45 (N=2076;2060)
    7
    13
        HPV-51 (N=2040;2045)
    23
    26
        HPV-52 (N=2029;2031)
    34
    31
        HPV-56 (N=2071;2054)
    11
    15
        HPV-58 (N=2067;2065)
    14
    13
        HPV-59 (N=2074;2055)
    7
    10
        HPV-66 (N=2058;2052)
    22
    16
        HPV-68 (N=2053;2057)
    13
    22
        HPV-31/45 (N=2091;2081)
    14
    28
        HPV-31/45/33/52/58 (N=2094;2083)
    65
    75
        HPV-39/45/59/68 (N=2094;2083)
    46
    54
        HPV-31/33/35/52/58 (N=2094;2083)
    64
    72
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2094;2083)
    118
    129
        HPV-HRW (N=2094;2083)
    145
    160
        HPV-HR (N=2094;2083)
    147
    194
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.
    End point description
    CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Note: Results for seropositive status were not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2168
    2146
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1852;1818)
    1
    6
        HPV-16, DNA- and sero- subjects (N=1507;1491)
    1
    5
        HPV-18, DNA- and sero- subjects (N=1565;1541)
    1
    2
        HPV-16/18, overall (N=2168;2146)
    1
    8
        HPV-16, overall (N=2112;2090)
    1
    5
        HPV-18, overall (N=2149;2122)
    1
    4
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in: - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2168
    2146
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1852;1818)
    2
    12
        HPV-16, DNA- and sero- subjects (N=1507;1491)
    1
    9
        HPV-18, DNA- and sero- subjects (N=1565;1541)
    2
    4
        HPV-16/18, DNA- and sero+ subjects (N=870;848)
    0
    3
        HPV-16, DNA- and sero+ subjects (N=588;583)
    0
    1
        HPV-18, DNA- and sero+ subjects (N=552;539)
    0
    2
        HPV-16/18, overall (N=2168;2146)
    2
    16
        HPV-16, overall (N=2112;2090)
    1
    10
        HPV-18, overall (N=2149;2122)
    2
    7
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection detected within the lesional component of the cervical tissue specimen.
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2733
    2735
    Units: Subjects
        HPV-16/18
    37
    66
        HPV-16
    26
    49
        HPV-18
    14
    23
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ irrespective of HPV cervical infection and irrespective of baseline HPV DNA status.

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    End point title
    		 Number of subjects with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ irrespective of HPV cervical infection and irrespective of baseline HPV DNA status.
    End point description
    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2733
    2735
    Units: Subjects
        Subjects
    179
    229
    No statistical analyses for this end point

    Secondary: Number of subjects with any cytological abnormalities associated with HPV-16 or HPV-18 cervical infection.

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    End point title
    		 Number of subjects with any cytological abnormalities associated with HPV-16 or HPV-18 cervical infection.
    End point description
    Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. Results for seropositive status were not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2168
    2146
    Units: Subjects
        HPV-16/18, DNA- and sero- subjects (N=1852;1818)
    3
    47
        HPV-16, DNA- and sero- subjects (N=1507;1491)
    3
    34
        HPV-18, DNA- and sero- subjects (N=1565;1541)
    0
    14
        HPV-16/18, overall (N=2168;2146)
    6
    56
        HPV-16 (N=2112;2090)
    5
    38
        HPV-18 (N=2149;2122)
    1
    19
    No statistical analyses for this end point

    Secondary: Number of subjects with cytological abnormalities associated with oncogenic HPV types individually or in combinations.

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    End point title
    		 Number of subjects with cytological abnormalities associated with oncogenic HPV types individually or in combinations.
    End point description
    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 .
    End point type
    Secondary
    End point timeframe
    Up to Month 48
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2169
    2146
    Units: Subjects
        HPV-16 (N=2112;2090)
    5
    38
        HPV-18 (N=2149;2122)
    1
    19
        HPV-31 (N=2117;2127)
    5
    23
        HPV-33 (N=2149;2130)
    6
    8
        HPV-35 (N=2156;2137)
    7
    13
        HPV-39 (N=2141;2114)
    21
    23
        HPV-45 (N=2150;2125)
    5
    23
        HPV-51 (N=2115;2107)
    38
    34
        HPV-52 (N=2103;2095)
    25
    22
        HPV-56 (N=2144;2115)
    15
    28
        HPV-58 (N=2142;2128)
    19
    13
        HPV-59 (N=2147;2120)
    9
    22
        HPV-66 (N=2133;2117)
    22
    43
        HPV-68 (N=2128;2120)
    15
    15
        HPV-31/45 (N=2165;2146)
    10
    44
        HPV-31/45/33/52/58 (N=2169;2148)
    56
    78
        HPV-39/45/59/68 (N=2169;2148)
    49
    74
        HPV-31/33/35/52/58 (N=2169;2148)
    56
    70
        HPV-31/45/33/52/58/35/39/51/56/59 (N=2169;2148)
    119
    160
        HPV-HRW (N=2169;2148)
    143
    192
        HPV-HR (N=2169;2148)
    145
    223
    No statistical analyses for this end point

    Secondary: Number of subjects with histopathologically confirmed reduction of local cervical therapy.

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    End point title
    		 Number of subjects with histopathologically confirmed reduction of local cervical therapy.
    End point description
    Detection was done on all subjects irrespective of their baseline HPV DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2733
    2735
    Units: Subjects
        Subjects
    88
    110
    No statistical analyses for this end point

    Secondary: Number of subjects with first colposcopy.

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    End point title
    		 Number of subjects with first colposcopy.
    End point description
    DNA status.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2734
    2736
    Units: Subjects
        Subjects
    506
    560
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection .

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with human papillomavirus (HPV)-16 or HPV-18 and/or with histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ associated with HPV-16 and/or -18 cervical infection .
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2768
    2778
    Units: Subjects
        HPV-16/18
    93
    209
        HPV-16
    66
    152
        HPV-18
    32
    71
    No statistical analyses for this end point

    Secondary: Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-confirmed CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).

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    End point title
    		 Number of subjects with persistent infection (6-month definition) with HPV-16 or HPV-18 and/or with histopathologically-confirmed CIN1+ associated with HPV-16 and/or -18 cervical infection detected using the HPV Type Assignment Algorithm (TAA).
    End point description
    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types).
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2768
    2778
    Units: Subjects
        HPV-16/18
    92
    206
        HPV-16
    65
    151
        HPV-18
    30
    68
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects against HPV-16 in the immunogenicity subset.

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    End point title
    		 Number of seroconverted subjects against HPV-16 in the immunogenicity subset.
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e.; titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-16 assay cut-off value was defined as greater than or equal to 8 ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region.
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 60, 72 and 84.
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    277
    260
    Units: Subjects
        Sero- at Month 60 (N=275;251)
    275
    11
        Sero- at Month 72 (N=277;260)
    276
    5
        Sero- at Month 84 (N=275;255)
    273
    2
        Sero+ at Month 60 (N=99,95)
    99
    79
        Sero+ at Month 72 (N=99,102)
    99
    57
        Sero+ at Month 84 (N=95,101)
    95
    51
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects against HPV-18 in the immunogenicity subset.

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    End point title
    		 Number of seroconverted subjects against HPV-18 in the immunogenicity subset.
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e.; titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-18 assay cut-off value was defined as greater than or equal to 7 ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region.
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 60, 72 and 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    269
    254
    Units: Subjects
        Sero- at Month 60 (N=268;246)
    266
    11
        Sero- at Month 72 (N=269;254)
    261
    3
        Sero- at month 84 (N=268;248)
    257
    3
        Sero+ at Month 60 (N=101;91)
    101
    58
        Sero+ at Month 72 (N=103;99)
    103
    32
        Sero+ at Month 84 (N=98;98)
    98
    32
    No statistical analyses for this end point

    Secondary: Geometric mean concentrations (GMCs) against HPV-16 antibody in the immunogenicity subset.

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    End point title
    		 Geometric mean concentrations (GMCs) against HPV-16 antibody in the immunogenicity subset.
    End point description
    GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region).
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 60, 72 and 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    277
    260
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Sero- at Month 60 (N=275;251)
    447.1 (394.3 to 507)
    4.3 (4.1 to 4.5)
        Sero- at Month 72 (N=277;260)
    412.8 (364 to 468.1)
    9.8 (9.5 to 10)
        Sero- at Month 84 (N=275;255)
    381 (334.7 to 433.8)
    9.6 (9.4 to 9.9)
        Sero+ at Month 60 (N=99;95)
    943 (749.2 to 1187)
    24.7 (24.7 to 31.7)
        Sero+ at Month 72 (N=99;102)
    1053.7 (841 to 1320.3)
    25.6 (20.7 to 31.5)
        Sero+ at Month 84 (N=95;101)
    954.3 (755.3 to 1205.8)
    23.9 (19.3 to 29.5)
    No statistical analyses for this end point

    Secondary: Geometric mean concentrations (GMCs) against HPV-18 antibody in the immunogenicity subset.

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    End point title
    		 Geometric mean concentrations (GMCs) against HPV-18 antibody in the immunogenicity subset.
    End point description
    GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region).
    End point type
    Secondary
    End point timeframe
    At pre-vaccination and at Month 60, 72 and 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    269
    254
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Sero- at Month 60 (N=268;246)
    174.3 (151.2 to 200.8)
    3.8 (3.6 to 4)
        Sero- at Month 72 (N=269;254)
    177.7 (154.1 to 204.8)
    9.2 (9 to 9.5)
        Sero- at Month 84 (N=268;248)
    166.2 (143.4 to 192.7)
    9.1 (9 to 9.3)
        Sero+ at Month 60 (N=101;91)
    306 (245.7 to 380.9)
    12.9 (9.8 to 16.9)
        Sero+ at Month 72 (N=103;99)
    324.8 (264.3 to 399.1)
    16.2 (13.3 to 19.6)
        Sero+ at Month 84 (N=98;98)
    302.2 (243.4 to 375.2)
    16.5 (13.4 to 20.4)
    No statistical analyses for this end point

    Secondary: Number of subjects reporting related or fatal serious adverse event.

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    End point title
    		 Number of subjects reporting related or fatal serious adverse event.
    End point 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.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2877
    2870
    Units: Subjects
        Fatal AEs
    13
    5
        Related SAEs
    5
    8
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any AE/SAE leading to premature discontinuation of the study.

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    End point title
    		 Number of subjects reporting any AE/SAE leading to premature discontinuation of the study.
    End point 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. 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.
    End point type
    Secondary
    End point timeframe
    Up to Month 84
    End point values
    		 Cervarix Group Aluminium Hydroxide Group
    Number of subjects analysed
    2877
    2870
    Units: Subjects
        AEs/SAEs
    28
    14
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs: from the beginning of the study up to Month 84. Unsolicited AEs: within 30 days (Days 0-29) post-vaccination period). Solicited AEs: During the 7-day (Days 0-6) post-vaccination period.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Aluminium Hydroxide Group
    Reporting group description
    		 Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Reporting group title
    Cervarix Group
    Reporting group description
    		 Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

    Serious adverse events
    		 Aluminium Hydroxide Group Cervarix Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    269 / 2871 (9.37%)
    291 / 2881 (10.10%)
         number of deaths (all causes)
    5
    13
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    9 / 2871 (0.31%)
    13 / 2881 (0.45%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    3 / 2871 (0.10%)
    4 / 2881 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ovarian adenoma
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    3 / 2871 (0.10%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of the cervix
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenoma benign
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaplastic astrocytoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer female
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer stage II
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix cancer metastatic
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibroma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hodgkin’s disease
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liposarcoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Mediastinum neoplasm
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngeal cancer
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal oncocytoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Teratoma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal adenocarcinoma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 2871 (0.07%)
    4 / 2881 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids thrombosed
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous complete
         subjects affected / exposed
    16 / 2871 (0.56%)
    19 / 2881 (0.66%)
         occurrences causally related to treatment / all
    2 / 16
    2 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion spontaneous incomplete
         subjects affected / exposed
    13 / 2871 (0.45%)
    18 / 2881 (0.62%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion missed
         subjects affected / exposed
    11 / 2871 (0.38%)
    10 / 2881 (0.35%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blighted ovum
         subjects affected / exposed
    7 / 2871 (0.24%)
    6 / 2881 (0.21%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion threatened
         subjects affected / exposed
    7 / 2871 (0.24%)
    4 / 2881 (0.14%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    3 / 2871 (0.10%)
    7 / 2881 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ectopic pregnancy
         subjects affected / exposed
    5 / 2871 (0.17%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Premature labour
         subjects affected / exposed
    2 / 2871 (0.07%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ruptured ectopic pregnancy
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrested labour
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gestational hypertension
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    12 / 2871 (0.42%)
    13 / 2881 (0.45%)
         occurrences causally related to treatment / all
    2 / 12
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Premature delivery
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion complete
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foetal death
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage in pregnancy
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperemesis gravidarum
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Placenta accreta
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postpartum haemorrhage
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retained products of conception
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stillbirth
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Threatened labour
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prolonged labour
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 2871 (0.00%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Anaphylactic reaction
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Homicide
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    6 / 2871 (0.21%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    3 / 2871 (0.10%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    3 / 2871 (0.10%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometriosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bartholin’s cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst torsion
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenomyosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adnexal torsion
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bartholinitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colpocele
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endosalpingiosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menometrorrhagia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic prolapse
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polycystic ovaries
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine atony
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterovaginal prolapse
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    2 / 2871 (0.07%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumothorax
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nasal cyst
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal disorder
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus disorder
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    1 / 2871 (0.03%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 2871 (0.00%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Bipolar disorder
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorexia nervosa
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    3 / 2871 (0.10%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaesthetic complication pulmonary
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropod sting
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone fissure
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post lumbar puncture syndrome
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulnar nerve injury
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Bronchogenic cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyloric stenosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Angina pectoris
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 2871 (0.00%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    4 / 2871 (0.14%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Altered state of consciousness
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral cyst
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic coma
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial haematoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoparesis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sedation
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery dissection
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Premature rupture of membranes
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Placental transfusion syndrome
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular oedema
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein thrombosis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 2871 (0.07%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 2871 (0.07%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiploic appendagitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedematous pancreatitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth impacted
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    9 / 2871 (0.31%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 2871 (0.07%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    3 / 2871 (0.10%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    3 / 2871 (0.10%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    2 / 2871 (0.07%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus bladder
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ureteric obstruction
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Addison’s disease
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basedow’s disease
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 2871 (0.07%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 2871 (0.10%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis reactive
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint instability
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint range of motion decreased
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lupus-like syndrome
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periostitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    12 / 2871 (0.42%)
    13 / 2881 (0.45%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 2871 (0.03%)
    9 / 2881 (0.31%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 2871 (0.10%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 2871 (0.10%)
    5 / 2881 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 2871 (0.03%)
    6 / 2881 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 2871 (0.03%)
    3 / 2881 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 2871 (0.03%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Salpingitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinusitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amniotic cavity infection
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burn infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chlamydial infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic tonsillitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis klebsiella
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genitourinary tract infection
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Opisthorchiasis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pasteurella infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic inflammatory disease
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Typhoid fever
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 2871 (0.03%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 2871 (0.03%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    3 / 2871 (0.10%)
    0 / 2881 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 2871 (0.00%)
    2 / 2881 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholesterosis
         subjects affected / exposed
    0 / 2871 (0.00%)
    1 / 2881 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Aluminium Hydroxide Group Cervarix Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1862 / 2871 (64.86%)
    2411 / 2881 (83.69%)
    Nervous system disorders
    Headache (unsolicited)
         subjects affected / exposed
    222 / 2871 (7.73%)
    203 / 2881 (7.05%)
         occurrences all number
    222
    203
    General disorders and administration site conditions
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1862 / 2871 (64.86%)
    2411 / 2881 (83.69%)
         occurrences all number
    1862
    2411
    Redness
    alternative assessment type: Systematic
         subjects affected / exposed
    530 / 2871 (18.46%)
    1058 / 2881 (36.72%)
         occurrences all number
    530
    1058
    Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    428 / 2871 (14.91%)
    1080 / 2881 (37.49%)
         occurrences all number
    428
    1080
    Arthralgia
    alternative assessment type: Systematic
         subjects affected / exposed
    439 / 2871 (15.29%)
    580 / 2881 (20.13%)
         occurrences all number
    439
    580
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    916 / 2871 (31.91%)
    1116 / 2881 (38.74%)
         occurrences all number
    916
    1116
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    248 / 2871 (8.64%)
    308 / 2881 (10.69%)
         occurrences all number
    248
    308
    Gastrointestinal
    alternative assessment type: Systematic
         subjects affected / exposed
    592 / 2871 (20.62%)
    664 / 2881 (23.05%)
         occurrences all number
    592
    664
    Headache (solicited general symptom)
    alternative assessment type: Systematic
         subjects affected / exposed
    1074 / 2871 (37.41%)
    1165 / 2881 (40.44%)
         occurrences all number
    1074
    1165
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    622 / 2871 (21.66%)
    878 / 2881 (30.48%)
         occurrences all number
    622
    878
    Rash
    alternative assessment type: Systematic
         subjects affected / exposed
    124 / 2871 (4.32%)
    185 / 2881 (6.42%)
         occurrences all number
    124
    185
    Urticaria
    alternative assessment type: Systematic
         subjects affected / exposed
    201 / 2871 (7.00%)
    258 / 2881 (8.96%)
         occurrences all number
    201
    258

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Aug 2006
    Study endpoints were amended following a request from the FDA and study procedures were amended following the licensure of an HPV vaccine by a competitor. In addition a safety interim analysis is now planned.
    30 Jul 2008
    The protocol has been amended to add an additional gynaecological examination, to enlarge the length of study visit intervals and to clarify the procedures for cross-over immunization and follow-up gynaecological care after study completion (as requested by the IDMC). In addition, a new Investigator's Brochure, Edition 8 dated August 2008, has been issued since the previous submission, which replaces the Investigator's Brochure, Edition 7 dated August 2007.
    23 Oct 2008
    As requested by the FDA, the principle analysis of efficacy endpoints will be performed on the according-to-protocol (ATP) cohort for efficacy, excluding the 15% subset of women enrolled with a prior history of HPV disease/infection. In order to maintain the power for the primary endpoint, two additional study visits (at Months 42 and 48) were added to extend the total study duration by 12 months.
    24 Mar 2010
    Because the HPV-015 study population is sexually active, it is important to also evaluate the vaccine efficacy in all women, including those who have been exposed to HPV (i.e., in the Total Vaccinated cohort [TVC]). In order to demonstrate this impact, the study protocol has been amended to extend by a maximum of three additional years, resulting in a maximum total length of seven years (84 months) follow-up.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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