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    Clinical Trial Results:
    A randomized, double-blind, double-dummy, parallel- group, multi-center phase IIb study to assess the efficacy and safety of different dose combinations of an aromatase inhibitor and a progestin in an intravaginal ring versus placebo and leuprorelin / leuprolide acetate in women with symptomatic endometriosis over a 12-week treatment period

    Summary
    EudraCT number
    		 2013-005090-53
    Trial protocol
    		 FI   CZ   DK   AT   BE   NL   PL   ES  
    Global end of trial date
    24 Oct 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Oct 2017
    First version publication date
    28 Oct 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BAY98-7196/15832
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02203331
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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
    Final
    Date of interim/final analysis
    24 Oct 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the dose-response relationship and demonstrate efficacy of BAY98-7196 versus placebo in women with symptomatic endometriosis.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Oct 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    Japan: 62
    Country: Number of subjects enrolled
    United States: 54
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    Norway: 5
    Country: Number of subjects enrolled
    Poland: 38
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    Austria: 11
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Czech Republic: 56
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    Finland: 12
    Country: Number of subjects enrolled
    Germany: 37
    Worldwide total number of subjects
    319
    EEA total number of subjects
    196
    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)
    319
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Study was conducted in fourteen countries in Austria, Belgium, Canada, Czech Republic, Denmark, Finland, Germany, Japan, Netherlands, Norway, Poland, Spain, Switzerland, United States, between 16 October 2014 (first subject first visit) and 24 October 2016 (last subject last visit).

    Pre-assignment
    Screening details
    		 Overall, 605 subjects were screened, of them 286 failed screening, remaining 319 subjects were randomized and allocated to treatment, of them 14 subjects did not receive study treatment for various reasons, remaining 305 subjects were treated and 272 subjects completed study treatment.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LNG 40 mcg IVR + Placebo Injection
    Arm description
    		 Subjects wore an intra-vaginal ring (IVR) of Levonorgestrel (LNG) 40 microgram (mcg) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin intramuscular (i.m.) injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levonorgestrel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of LNG 40 mcg continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Placebo Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Arm title
    		 ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection
    Arm description
    		 Subjects wore IVR of Anastrozole (ATZ) 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anastrozole + Levonorgestrel
    Investigational medicinal product code
    BAY98-7196
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of ATZ 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Placebo Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Arm title
    		 ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection
    Arm description
    		 Subjects wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anastrozole + Levonorgestrel
    Investigational medicinal product code
    BAY98-7196
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Placebo Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Arm title
    		 ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection
    Arm description
    		 Subjects wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anastrozole + Levonorgestrel
    Investigational medicinal product code
    BAY98-7196
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Placebo Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Arm title
    		 Placebo IVR + Leuprorelin Injection
    Arm description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of 11.25 milligram (mg) leuprorelin i.m. injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo IVR
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Leuprorelin Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of 11.25 mg leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Arm title
    		 Placebo IVR + Placebo Injection
    Arm description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo IVR
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Vaginal delivery system
    Routes of administration
    Vaginal use
    Dosage and administration details
    Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days.

    Investigational medicinal product name
    Placebo Injection
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Number of subjects in period 1
    		LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Started
    52
    53
    55
    53
    53
    53
    Treated
    49
    50
    54
    49
    50
    53
    Completed
    45
    39
    50
    46
    46
    46
    Not completed
    7
    14
    5
    7
    7
    7
         Consent withdrawn by subject
    1
    -
    1
    -
    -
    3
         Protocol violation
    -
    2
    -
    1
    1
    -
         Other
    1
    2
    -
    2
    -
    -
         Pregnancy
    1
    -
    -
    -
    2
    -
         Adverse event
    4
    8
    3
    4
    3
    3
         Lost to follow-up
    -
    -
    -
    -
    1
    -
         Lack of efficacy
    -
    2
    1
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore an intra-vaginal ring (IVR) of Levonorgestrel (LNG) 40 microgram (mcg) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin intramuscular (i.m.) injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of Anastrozole (ATZ) 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    Placebo IVR + Leuprorelin Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of 11.25 milligram (mg) leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    Placebo IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection Total
    Number of subjects
    		 52 53 55 53 53 53 319
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 33.27 ± 7.4 32.96 ± 8.79 33.96 ± 5.73 33.72 ± 7.85 33.7 ± 6.29 34.89 ± 7.13 -
    Gender categorical
    Units: Subjects
        Female
    		 52 53 55 53 53 53 319
    Body Mass Index (BMI)
    Body mass index was an estimate of body fat based on body weight divided by height.
    Units: kilogram per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    		 24.19 ± 4.52 26.07 ± 6.71 23.84 ± 6.15 25.47 ± 5.68 25.47 ± 5.51 24.43 ± 5.08 -
    Mean Pain of the 7 Days With Worst Endometriosis Associated Pelvic Pain (EAPP)
    Pain intensity was assessed on 11-point (0-10) numerical rating scale (NRS) by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in an endometriosis symptom diary (ESD). The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7. Here, (n=39, 34, 42, 35, 40, 39) for mean pain of the 7 days with worst EAPP.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 7.8205 ± 1.171 7.4664 ± 0.9893 8.1905 ± 1.068 7.5429 ± 1.2568 7.8964 ± 1.1952 7.6886 ± 1.2389 -
    Percentage of Days With Pain Greater Than or Equal to (>=) 7
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=7 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that 28-day window where item 1 of the ESD was >=7. Here, (n=39, 34, 42, 35, 40, 39) for percentage of days with pain >=7.
    Units: percentage of days
        arithmetic mean (standard deviation)
    		 50.094 ± 35.5201 40.1521 ± 29.8714 55.1155 ± 33.7625 37.3044 ± 30.2894 48.7001 ± 33.6685 41.1847 ± 33.0479 -
    Percentage of Days With Pain >=4
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=4 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that window where Item 1 of the ESD was >=4. Here, (n=39, 34, 42, 35, 40, 39) for percentage of days with pain >=4.
    Units: percentage of days
        arithmetic mean (standard deviation)
    		 86.0058 ± 19.3136 84.7239 ± 18.1713 89.029 ± 16.3667 85.8451 ± 17.9466 92.9141 ± 11.6008 80.4397 ± 20.1004 -

    End points

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    End points reporting groups
    Reporting group title
    LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore an intra-vaginal ring (IVR) of Levonorgestrel (LNG) 40 microgram (mcg) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin intramuscular (i.m.) injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of Anastrozole (ATZ) 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    Placebo IVR + Leuprorelin Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of 11.25 milligram (mg) leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Reporting group title
    Placebo IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjects were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.

    Subject analysis set title
    Per Protocol Set (PPS)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    PPS (N=232) included all full analysis set subjects diagnosed by surgery who had no major protocol violations.

    Primary: Absolute Change in Mean Pain of the 7Days With Worst EAPP From Baseline (Last 28Days Before Randomization) to End of Treatment (Last 28Days of Treatment Period,Days 57-84) as Measured on NRS by Question 1 of ESD

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    End point title
    		 Absolute Change in Mean Pain of the 7Days With Worst EAPP From Baseline (Last 28Days Before Randomization) to End of Treatment (Last 28Days of Treatment Period,Days 57-84) as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7.
    End point type
    Primary
    End point timeframe
    Baseline (last 28 days before randomization), end of treatment (Treatment 3) (last 28 days of the treatment period, Day 57-84)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    39 [1]
    33 [2]
    42 [3]
    35 [4]
    40 [5]
    39 [6]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -1.8974 ± 1.6416
    -1.6061 ± 1.6652
    -2.4014 ± 2.1833
    -2.2653 ± 1.5972
    -3.7679 ± 2.3507
    -2.293 ± 1.8247
    Notes
    [1] - PPS with evaluable subjects for this endpoint.
    [2] - PPS with evaluable subjects for this endpoint.
    [3] - PPS with evaluable subjects for this endpoint.
    [4] - PPS with evaluable subjects for this endpoint.
    [5] - PPS with evaluable subjects for this endpoint.
    [6] - PPS with evaluable subjects for this endpoint.
    Statistical analysis title
    		 Statistical analysis for Emax
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3875
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2925
    Statistical analysis title
    		 Statistical analysis for Linear
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2676
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2975
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 1
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3211
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2922
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 2
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1721
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2994

    Secondary: Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment (Day 1-28) and to Second Cycle Under Study Treatment (Day 29-56) as Measured on NRS by Question 1 of ESD

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    End point title
    		 Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment (Day 1-28) and to Second Cycle Under Study Treatment (Day 29-56) as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    39 [7]
    34 [8]
    42 [9]
    35 [10]
    40 [11]
    39 [12]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Change at Treatment 1
    -0.7582 ± 1.1518
    -0.6849 ± 1.3832
    -1.1463 ± 1.3992
    -1 ± 1.2579
    -1.2071 ± 1.1978
    -0.9048 ± 1.1686
        Change at Treatment 2
    -1.6447 ± 1.4831
    -1.5126 ± 2.0161
    -2.1224 ± 2.2791
    -1.9959 ± 1.3978
    -2.8607 ± 2.0665
    -1.8022 ± 1.5131
    Notes
    [7] - PPS with evaluable subjects for this endpoint.
    [8] - PPS with evaluable subjects for this endpoint.
    [9] - PPS with evaluable subjects for this endpoint.
    [10] - PPS with evaluable subjects for this endpoint.
    [11] - PPS with evaluable subjects for this endpoint.
    [12] - PPS with evaluable subjects for this endpoint.
    Statistical analysis title
    		 Statistical analysis for Emax
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.231
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2878
    Statistical analysis title
    		 Statistical analysis for Linear
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1865
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2927
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 1
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1955
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2875
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 2
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1416
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2944

    Secondary: Absolute Change in Mean Pain From Baseline(Last 28Days Before Randomization) to First Cycle Under Study Treatment(Day1-28),Second Cycle Under Study Treatment(Day29-56),Third Cycle Under Study Treatment(Day57-84) as Measured on NRS by Question1 of ESD

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    End point title
    		 Absolute Change in Mean Pain From Baseline(Last 28Days Before Randomization) to First Cycle Under Study Treatment(Day1-28),Second Cycle Under Study Treatment(Day29-56),Third Cycle Under Study Treatment(Day57-84) as Measured on NRS by Question1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain within a 28-day window was calculated as the sum of ESD item 1 within that 28-day window divided by the number with non-missing days within that 28-day window. Here, number of subjects 'n' signifies evaluable subjects for the respective category.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56), and third cycle (Treatment 3) (last 28 days of the treatment period, Day 57-84)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    39 [13]
    34 [14]
    42 [15]
    35 [16]
    40 [17]
    39 [18]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n=39,34,42,35,40,39)
    6.0938 ± 1.5314
    5.7409 ± 1.3044
    6.3694 ± 1.53
    5.7128 ± 1.4415
    6.3962 ± 1.4575
    5.6399 ± 1.5312
        Change at Treatment 1 (n=39,34,42,35,40,39)
    -0.8472 ± 1.1905
    -0.9009 ± 1.3434
    -1.0931 ± 1.4002
    -1.1257 ± 1.3317
    -1.5315 ± 1.4809
    -0.9777 ± 1.068
        Change at Treatment 2 (n=39,34,42,35,40,39)
    -1.5774 ± 1.6278
    -1.5068 ± 1.8707
    -1.7349 ± 1.9403
    -1.9615 ± 1.3966
    -2.6855 ± 2.0601
    -1.8994 ± 1.3069
        Change at Treatment 3 (n=39,33,42,35,40,39)
    -1.8001 ± 1.7687
    -1.6411 ± 1.8071
    -2.0112 ± 1.9575
    -2.1268 ± 1.6877
    -3.502 ± 2.3096
    -2.2228 ± 1.4957
    Notes
    [13] - PPS with evaluable subjects for this endpoint.
    [14] - PPS with evaluable subjects for this endpoint.
    [15] - PPS with evaluable subjects for this endpoint.
    [16] - PPS with evaluable subjects for this endpoint.
    [17] - PPS with evaluable subjects for this endpoint.
    [18] - PPS with evaluable subjects for this endpoint.
    Statistical analysis title
    		 Statistical analysis for Emax
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5794
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2832
    Statistical analysis title
    		 Statistical analysis for Linear
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4301
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.288
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 1
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5337
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2829
    Statistical analysis title
    		 Statistical analysis for Sigmoidal Emax 2
    Statistical analysis description
    The analysis was performed by using MCP-Mod method using pre-defined candidate dose-response model.
    Comparison groups
    LNG 40 mcg IVR + Placebo Injection v ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection v ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection v Placebo IVR + Placebo Injection
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3396
    Method
    		 Contrast tests for dose-response model
    Confidence interval
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2899

    Secondary: Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain Greater Than or Equal to (>=) 7 as Measured on NRS by Question 1 of ESD as Measured on NRS by Question 1 of ESD

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    End point title
    		 Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain Greater Than or Equal to (>=) 7 as Measured on NRS by Question 1 of ESD as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=7 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that 28-day window where item 1 of the ESD was >=7.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    41 [19]
    34 [20]
    42 [21]
    35 [22]
    41 [23]
    39 [24]
    Units: percentage of days
    arithmetic mean (standard deviation)
        Treatment 1 (n=41,34,42,35,41,39)
    35.6034 ± 34.3126
    27.5659 ± 27.6426
    40.0813 ± 37.2694
    23.9322 ± 28.6234
    28.2015 ± 28.843
    25.1742 ± 24.2811
        Treatment 2 (n=41,34,42,35,41,39)
    25.6257 ± 33.9315
    22.8695 ± 28.3443
    34.4364 ± 40.5623
    14.9331 ± 23.8028
    12.132 ± 25.1638
    14.1869 ± 17.7364
        Treatment 3 (n=41,33,42,35,41,39)
    23.1293 ± 33.9451
    19.9332 ± 26.054
    29.8103 ± 39.0434
    14.3362 ± 25.677
    8.5351 ± 20.7819
    12.7574 ± 18.5154
    Notes
    [19] - PPS with evaluable subjects for this endpoint.
    [20] - PPS with evaluable subjects for this endpoint.
    [21] - PPS with evaluable subjects for this endpoint.
    [22] - PPS with evaluable subjects for this endpoint.
    [23] - PPS with evaluable subjects for this endpoint.
    [24] - PPS with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=7 as Measured on NRS by Question 1 of ESD

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    End point title
    		 Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=7 as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=7 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that 28-day window where item 1 of the ESD was >=7. Here, number of subjects 'n' signifies evaluable subjects for the respective category.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    39 [25]
    34 [26]
    42 [27]
    35 [28]
    40 [29]
    39 [30]
    Units: percentage of days
    arithmetic mean (standard deviation)
        Change at Treatment 1 (n=39,34,42,35,40,39)
    -13.6756 ± 22.6822
    -12.5862 ± 21.4336
    -15.0341 ± 21.0071
    -13.3722 ± 19.6416
    -19.8898 ± 25.9273
    -16.0105 ± 19.019
        Change at Treatment 2 (n=39,34,42,35,40,39)
    -24.1404 ± 28.5082
    -17.2826 ± 29.0007
    -20.6791 ± 30.2152
    -22.3713 ± 24.4098
    -36.354 ± 34.9706
    -26.9979 ± 24.9493
        Change at Treatment 3 (n=39,33,42,35,40,39)
    -26.4197 ± 31.4648
    -20.8529 ± 28.3939
    -25.3052 ± 33.5497
    -22.9682 ± 28.8677
    -39.9516 ± 33.8277
    -28.4273 ± 29.6186
    Notes
    [25] - PPS with evaluable subjects for this endpoint.
    [26] - PPS with evaluable subjects for this endpoint.
    [27] - PPS with evaluable subjects for this endpoint.
    [28] - PPS with evaluable subjects for this endpoint.
    [29] - PPS with evaluable subjects for this endpoint.
    [30] - PPS with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain >=4 as Measured on NRS by Question 1 of ESD

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    End point title
    		 Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain >=4 as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=4 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that window where Item 1 of the ESD was >=4. Here, number of subjects 'n' signifies evaluable subjects for the respective category.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    41 [31]
    34 [32]
    42 [33]
    35 [34]
    41 [35]
    39 [36]
    Units: percentage of days
    arithmetic mean (standard deviation)
        Treatment 1 (n=41, 34, 42, 35, 41, 39)
    71.8037 ± 32.3658
    69.3092 ± 27.8642
    73.8956 ± 31.6868
    70.6504 ± 27.8528
    70.2066 ± 28.9333
    65.9074 ± 30.0166
        Treatment 2 (n=41, 34, 42, 35, 41, 39)
    61.8199 ± 37.1217
    57.8777 ± 34.7429
    62.5822 ± 37.6989
    52.6028 ± 35.6106
    54.0965 ± 38.9629
    49.487 ± 31.3566
        Treatment 3 (n=41, 33, 42, 35, 41, 39)
    60.2902 ± 37.8585
    57.0171 ± 34.3642
    56.7691 ± 40.3803
    50.7332 ± 36.2903
    38.6986 ± 39.6045
    47.0976 ± 35.3227
    Notes
    [31] - PPS with evaluable subjects for this endpoint.
    [32] - PPS with evaluable subjects for this endpoint.
    [33] - PPS with evaluable subjects for this endpoint.
    [34] - PPS with evaluable subjects for this endpoint.
    [35] - PPS with evaluable subjects for this endpoint.
    [36] - PPS with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=4 as Measured on NRS by Question 1 of ESD

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    End point title
    		 Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=4 as Measured on NRS by Question 1 of ESD
    End point description
    Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=4 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that window where Item 1 of the ESD was >=4. Here, number of subjects 'n' signifies evaluable subjects for the respective category.
    End point type
    Secondary
    End point timeframe
    Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
    End point values
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin Injection Placebo IVR + Placebo Injection
    Number of subjects analysed
    39 [37]
    34 [38]
    42 [39]
    35 [40]
    40 [41]
    39 [42]
    Units: percentage of days
    arithmetic mean (standard deviation)
        Change at Treatment 1 (n=39,34,42,35,40,39)
    -12.8228 ± 20.433
    -15.4147 ± 24.0608
    -15.1334 ± 22.5347
    -15.1947 ± 21.174
    -21.4331 ± 23.4546
    -14.5323 ± 20.967
        Change at Treatment 2 (n=39,34,42,35,40,39)
    -22.495 ± 28.1535
    -26.8462 ± 32.6194
    -26.4468 ± 34.4661
    -33.2423 ± 27.3686
    -37.733 ± 36.9484
    -30.9527 ± 25.4665
        Change at Treatment 3 (n=39,33,42,35,40,39)
    -23.5498 ± 30.2853
    -27.477 ± 34.2051
    -32.26 ± 37.4997
    -35.1119 ± 30.9316
    -53.4266 ± 38.8452
    -33.3421 ± 25.7105
    Notes
    [37] - PPS with evaluable subjects for this endpoint.
    [38] - PPS with evaluable subjects for this endpoint.
    [39] - PPS with evaluable subjects for this endpoint.
    [40] - PPS with evaluable subjects for this endpoint.
    [41] - PPS with evaluable subjects for this endpoint.
    [42] - PPS with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study treatment up to 30 days after end of treatment (Day 114)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of LNG 40 mcg continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. single dose of placebo matched to leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Reporting group title
    ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. single dose of placebo matched to leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Reporting group title
    ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. single dose of placebo matched to leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Reporting group title
    ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. single dose of placebo matched to leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Reporting group title
    Placebo IVR + Leuprorelin 11.25 mg Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. a single dose of 11.25 mg leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Reporting group title
    Placebo IVR + Placebo Injection
    Reporting group description
    		 Subjects wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and subjs were admin. a single dose of placebo matched to leuprorelin i.m. injn. (3 month depot) on the first day of trtmt.

    Serious adverse events
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin 11.25 mg Injection Placebo IVR + Placebo Injection
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    3 / 50 (6.00%)
    4 / 53 (7.55%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy of unknown location
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometriosis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic ovarian cyst
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dyshidrotic eczema
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal atrophy
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pyelonephritis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 LNG 40 mcg IVR + Placebo Injection ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection Placebo IVR + Leuprorelin 11.25 mg Injection Placebo IVR + Placebo Injection
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    38 / 49 (77.55%)
    40 / 50 (80.00%)
    40 / 54 (74.07%)
    35 / 49 (71.43%)
    35 / 50 (70.00%)
    38 / 53 (71.70%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Schwannoma
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    2 / 54 (3.70%)
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    2
    0
    2
    0
    Ovarian adenoma
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Haematoma
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hot flush
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    3 / 54 (5.56%)
    3 / 49 (6.12%)
    17 / 50 (34.00%)
    2 / 53 (3.77%)
         occurrences all number
    1
    0
    3
    3
    26
    2
    Surgical and medical procedures
    Wisdom teeth removal
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 49 (0.00%)
    3 / 50 (6.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    3
    1
    1
    0
    2
    Feeling hot
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Hunger
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Malaise
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Oedema
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Pelvic mass
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Swelling
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    Medical device discomfort
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Haemorrhagic cyst
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Medical device site discomfort
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Breast cyst
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Breast enlargement
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Breast pain
         subjects affected / exposed
    2 / 49 (4.08%)
    2 / 50 (4.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    2
    2
    1
    0
    2
    0
    Breast tenderness
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    0
    0
    1
    1
    3
    Dyspareunia
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    3 / 50 (6.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    0
    0
    4
    0
    Endometriosis
         subjects affected / exposed
    3 / 49 (6.12%)
    2 / 50 (4.00%)
    3 / 54 (5.56%)
    2 / 49 (4.08%)
    2 / 50 (4.00%)
    5 / 53 (9.43%)
         occurrences all number
    3
    2
    4
    2
    3
    5
    Fibrocystic breast disease
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Galactorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hydrosalpinx
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hypomenorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Menorrhagia
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    1
    2
    1
    0
    Menstruation irregular
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    Metrorrhagia
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    2 / 54 (3.70%)
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    2
    3
    1
    0
    Ovarian cyst
         subjects affected / exposed
    20 / 49 (40.82%)
    20 / 50 (40.00%)
    24 / 54 (44.44%)
    16 / 49 (32.65%)
    5 / 50 (10.00%)
    7 / 53 (13.21%)
         occurrences all number
    25
    21
    28
    22
    5
    9
    Ovarian rupture
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pelvic pain
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    2 / 54 (3.70%)
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    1
    1
    2
    2
    0
    2
    Polymenorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Uterine haemorrhage
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    3
    0
    3
    0
    0
    0
    Uterine polyp
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Uterine prolapse
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    0
    2
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 49 (2.04%)
    3 / 50 (6.00%)
    2 / 54 (3.70%)
    4 / 49 (8.16%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    5
    2
    7
    0
    0
    Vaginal odour
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Varicose veins pelvic
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vulvovaginal discomfort
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    4 / 50 (8.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    1
    0
    4
    1
    Breast discomfort
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    Adenomyosis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    Adnexa uteri pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Haemorrhagic ovarian cyst
         subjects affected / exposed
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    0
    Genital haemorrhage
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    Uterine haematoma
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vaginal flatulence
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vulvovaginal pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Abnormal withdrawal bleeding
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sinus congestion
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Depression
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    3
    0
    Irritability
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Libido decreased
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    4 / 50 (8.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    0
    4
    0
    Loss of libido
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Mood altered
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    Mood swings
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    2 / 54 (3.70%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    1
    1
    2
    0
    0
    2
    Depressive symptom
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Affect lability
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Product issues
    Device breakage
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Device expulsion
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Alanine aminotransferase abnormal
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 49 (2.04%)
    2 / 50 (4.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    2
    2
    0
    0
    0
    1
    Aspartate aminotransferase abnormal
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Colonoscopy
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood urine present
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Prothrombin time shortened
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Red blood cells urine positive
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Weight increased
         subjects affected / exposed
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    1
    1
    0
    1
    White blood cells urine positive
         subjects affected / exposed
    3 / 49 (6.12%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Urine bilirubin increased
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nitrite urine present
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Protein urine present
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Urine ketone body present
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Smear vaginal abnormal
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Gardnerella test positive
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Arthropod sting
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Epicondylitis
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Road traffic accident
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Muscle strain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Wound
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Post-traumatic pain
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Bone contusion
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Closed globe injury
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Nervous system disorders
    Burning sensation
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    0
    1
    0
    2
    3
    Headache
         subjects affected / exposed
    5 / 49 (10.20%)
    8 / 50 (16.00%)
    3 / 54 (5.56%)
    8 / 49 (16.33%)
    8 / 50 (16.00%)
    6 / 53 (11.32%)
         occurrences all number
    9
    8
    3
    9
    13
    6
    Migraine
         subjects affected / exposed
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    Haemorrhagic disorder
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Lymph node pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Deafness transitory
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eyelid rash
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    1
    0
    2
    0
    Abdominal pain
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    4 / 49 (8.16%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    2
    1
    4
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Constipation
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    0
    1
    0
    1
    3
    Diarrhoea
         subjects affected / exposed
    0 / 49 (0.00%)
    3 / 50 (6.00%)
    0 / 54 (0.00%)
    3 / 49 (6.12%)
    1 / 50 (2.00%)
    4 / 53 (7.55%)
         occurrences all number
    0
    3
    0
    3
    1
    4
    Dyspepsia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Enteritis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Gastritis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    2 / 49 (4.08%)
    2 / 50 (4.00%)
    2 / 54 (3.70%)
    4 / 49 (8.16%)
    3 / 50 (6.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    2
    2
    4
    3
    4
    Periodontal disease
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Toothache
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Dyschezia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Noninfectious peritonitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Faeces soft
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    2 / 53 (3.77%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    5 / 49 (10.20%)
    1 / 50 (2.00%)
    2 / 53 (3.77%)
         occurrences all number
    2
    1
    1
    5
    2
    2
    Alopecia
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dermatitis bullous
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Dry skin
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Purpura
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pruritus generalised
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hand dermatitis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    0
    1
    0
    1
    1
    Back pain
         subjects affected / exposed
    2 / 49 (4.08%)
    2 / 50 (4.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    3
    2
    0
    1
    1
    0
    Groin pain
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal disorder
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Muscle tightness
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Infections and infestations
    Bacterial vaginosis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    2 / 54 (3.70%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    2
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    1 / 54 (1.85%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    1
    1
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cystitis
         subjects affected / exposed
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    2 / 54 (3.70%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    3
    1
    2
    1
    0
    1
    Ear infection
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    2 / 54 (3.70%)
    1 / 49 (2.04%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    2
    1
    2
    0
    Hordeolum
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 49 (0.00%)
    2 / 50 (4.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    3 / 50 (6.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    2
    0
    1
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 49 (4.08%)
    2 / 50 (4.00%)
    7 / 54 (12.96%)
    5 / 49 (10.20%)
    1 / 50 (2.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    2
    8
    5
    1
    4
    Oral candidiasis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Periodontitis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pulpitis dental
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Sinusitis
         subjects affected / exposed
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    2 / 50 (4.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    0
    0
    1
    2
    0
    Tonsillitis
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    3 / 54 (5.56%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    3
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    Urethritis
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 49 (2.04%)
    2 / 50 (4.00%)
    2 / 54 (3.70%)
    1 / 49 (2.04%)
    1 / 50 (2.00%)
    2 / 53 (3.77%)
         occurrences all number
    1
    2
    3
    1
    1
    3
    Vulvovaginal candidiasis
         subjects affected / exposed
    2 / 49 (4.08%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Nail infection
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Borrelia infection
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    2 / 49 (4.08%)
    1 / 50 (2.00%)
    2 / 54 (3.70%)
    1 / 49 (2.04%)
    2 / 50 (4.00%)
    2 / 53 (3.77%)
         occurrences all number
    3
    1
    2
    1
    2
    2
    Metabolism and nutrition disorders
    Fluid retention
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Increased appetite
         subjects affected / exposed
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 54 (0.00%)
    0 / 49 (0.00%)
    1 / 50 (2.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Iron deficiency
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    0 / 54 (0.00%)
    1 / 49 (2.04%)
    0 / 50 (0.00%)
    0 / 53 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Decreased appetite
         subjects affected / exposed
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 54 (1.85%)
    0 / 49 (0.00%)
    0 / 50 (0.00%)
    1 / 53 (1.89%)
         occurrences all number
    0
    0
    1
    0
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Dec 2014
    This amendment was issued for - A more detailed specification of the Japanese subjects diagnosed by imaging was provided in inclusion criterion, based on local amendment for Japan. - The number of Japanese subjects diagnosed by imaging was changed based on local Japanese amendment, this number was reduced to 30 subjects and became identical to the number of Japanese subjects diagnosed by surgery. Consequently, the total number of subjects was updated. - The additions and rearrangement in the plan for statistical analysis described in the local amendment for Japan were incorporated into the global amendment. - Collection of data on the condom use was introduced, following a request from the Device Division of food and drug administration (FDA) to collect functional outcome data on condom use while intravaginal rings were worn by the subjects. - Hormone tests were removed from the safety laboratory analysis and added to “other variables and evaluations”. - Text related to subject information and informed consent was updated based on the new Informed Consent standard operating procedure (SOP).
    05 Jun 2015
    This amendment was issued for - The wording of exclusion criterion (“History of, and current anxiety and/or depression disorder”) was changed to “Current unstable anxiety and/or depression disorder (stable, well-managed symptoms of anxiety or mood disorders including depression are not exclusionary)”.

    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.
    Occurrence of "±” in relation with geometric CV is auto-generated and cannot be deleted. Decimal places were automatically truncated if last decimal equals zero.
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    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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