Clinical Trial Results:
Multi-center, single-arm study to assess the safety, efficacy, discontinuation rate and pharmacokinetics of the low-dose levonorgestrel intrauterine contraceptive system (LCS12) in post-menarcheal female adolescents under 18 years of age for 1 year, and an optional 2-year extension phase
Summary
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EudraCT number |
2011-002065-37 |
Trial protocol |
SE FI NL AT BE DE DK NO |
Global end of trial date |
28 May 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
04 Sep 2016
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First version publication date |
02 Jul 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY86-5028/14371
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01434160 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368, Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000606-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 May 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 May 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to assess the safety of the low-dose levonorgestrel (LNG) (12 microgram [mcg]/24 hour [h]) intrauterine contraceptive system (LCS12) in adolescents over 1 year of treatment, including the insertion and removal procedures.
The objective of the 2-year extension phase was to evaluate safety and efficacy of LCS12 during the intended duration of use, that is, for up to 3 years.
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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 and/or their legally authorized representatives. Participating subjects and/or their legally authorized representatives 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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Sep 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 64
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Country: Number of subjects enrolled |
Germany: 64
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Country: Number of subjects enrolled |
Austria: 63
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Country: Number of subjects enrolled |
Denmark: 17
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Country: Number of subjects enrolled |
Finland: 23
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Country: Number of subjects enrolled |
Netherlands: 55
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Country: Number of subjects enrolled |
Norway: 4
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Country: Number of subjects enrolled |
Sweden: 14
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Worldwide total number of subjects |
304
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EEA total number of subjects |
304
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
302
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Adults (18-64 years) |
2
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted at 36 study centers for 1 year treatment phase and 34 study centers for 2 year extension phase in 8 countries, from 26 September 2011 (first subject first visit) to 28 May 2015 (last subject last visit). | ||||||||||||||||||||||
Pre-assignment
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Screening details |
Overall 343 subjects were enrolled in the study, of which 304 were assigned to treatment. Thirty nine (39) subjects were excluded at screening, of which 26 were screening failures, 5 were withdrew consent, 4 were lost to follow-up, 2 due to adverse events, and 2 for other reasons. | ||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment Phase
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
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Arm title
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Levonorgestrel (BAY86-5028) | ||||||||||||||||||||||
Arm description |
Subjects received levonorgestrel (LNG) intrauterine contraceptive system with an initial in vitro release rate of 12 microgram LNG/day (LCS12) for up to 12 months. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Levonorgestrel
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Investigational medicinal product code |
BAY86-5028
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Other name |
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Pharmaceutical forms |
Intrauterine delivery system
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Routes of administration |
Intrauterine use
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Dosage and administration details |
The total LNG content in LCS12 was 13.5 mg. LCS12 was inserted into the uterus and could remain in place for up to 12 months.
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Period 2
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Period 2 title |
Extension Phase
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Is this the baseline period? |
No | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
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Arm title
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Levonorgestrel (BAY86-5028) | ||||||||||||||||||||||
Arm description |
Subjects received LCS12 for 12 months with an optional extension phase for further 24 months. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Levonorgestrel
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Investigational medicinal product code |
BAY86-5028
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Other name |
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Pharmaceutical forms |
Intrauterine delivery system
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Routes of administration |
Intrauterine use
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Dosage and administration details |
Subjects received LCS12 for 12 months with an optional extension phase for further 24 months.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Phase
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Reporting group description |
Subjects received LCS12 for 12 months with optional extension of 24 months. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Levonorgestrel (BAY86-5028)
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Reporting group description |
Subjects received levonorgestrel (LNG) intrauterine contraceptive system with an initial in vitro release rate of 12 microgram LNG/day (LCS12) for up to 12 months. | ||
Reporting group title |
Levonorgestrel (BAY86-5028)
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Reporting group description |
Subjects received LCS12 for 12 months with an optional extension phase for further 24 months. | ||
Subject analysis set title |
Full analysis set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
FAS included all subjects who had the LCS12 inserted or had at least an insertion attempt (successful or unsuccessful).
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End point title |
Percentage of Subjects With Treatment-Emergent Adverse Events During Treatment Phase [1] | ||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An /serious adverse events (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as AEs/SAEs that started or worsened after the study drug treatment.
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End point type |
Primary
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End point timeframe |
From the start of study treatment up to 12 months
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [2] - FAS |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Treatment-Emergent Adverse Events During Overall Study [3] | ||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An /serious adverse events (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as AEs/SAEs that started or worsened after the study drug treatment.
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End point type |
Primary
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End point timeframe |
From start of study treatment until 36 months (end of extension phase)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [4] - FAS |
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No statistical analyses for this end point |
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End point title |
Overall Satisfaction Rating by the 5-Point Likert Item at Month 12 | ||||||||||||||||||
End point description |
Satisfaction was assessed by the subject based on a 5-point Likert item, using the following question: How satisfied are you with the birth control method used during the study? and the answers were any of the following: 1. Very satisfied 2. Satisfied 3. Neither satisfied nor dissatisfied 4. Dissatisfied 5. Very dissatisfied. The overall satisfaction rate was the percentage of subjects selecting “1. Very satisfied” or “2. Satisfied” for the above question.
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End point type |
Secondary
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End point timeframe |
At Month 12
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Notes [5] - FAS |
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No statistical analyses for this end point |
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End point title |
Contraceptive Efficacy - Pearl Index | ||||||||||||||||||||
End point description |
The pearl index was defined as the number of pregnancies per 100 woman years. The following PIs were calculated: First year PI, Second year PI, Third year PI, 2-year PI, 3-year PI and Overall PI. Given the assumption that the number of pregnancies follows a Poisson distribution, the Pearl Index thus is the mean of this distribution. In the table below, "n" signifies the number of subjects evaluable at the corresponding time points.
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End point type |
Secondary
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End point timeframe |
From start of study treatment up to 3 years
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Notes [6] - FAS |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 28-day Reference Periods - Reference Period 1 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). Spotting episode (SE) means day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days. Spotting only episodes (SOE) means day(s) with spotting preceded and followed by at least 2 bleeding-free days and Bleeding/spotting-free interval means at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day.
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End point type |
Secondary
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End point timeframe |
At reference period 1 (1 reference period=28-days) during 1-year treatment phase
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Notes [7] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 28-day Reference Periods - Reference Period 5 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience).
For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 5 (1 reference period=28-days) during 1-year treatment phase
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Notes [8] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 28-day Reference Periods - Reference Period 9 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 9 (1 reference period=28-days) during 1-year treatment phase
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Notes [9] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 28-day Reference Periods - Reference Period 13 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 13 (1 reference period=28-days) during 1-year treatment phase
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Notes [10] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 1 (1 reference period=90-days) during 1-year treatment phase
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Notes [11] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 2 (1 reference period=90-days) during 1-year treatment phase
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Notes [12] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 3 (1 reference period=90-days) during 1-year treatment phase
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Notes [13] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | ||||||||||||||
End point description |
The occurrence of vaginal bleeding was to be recorded by study subjects every day in an e-diary. Bleeding intensity was categorized as: no vaginal bleeding, spotting (less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection except for panty liners), light (less than associated with normal menstruation relative to the subject’s experience with need for sanitary protection), normal (similar to normal menstruation relative to the subject’s experience) and heavy (more than normal menstruation relative to the subject’s experience). For Bleeding/spotting-free interval at least 2 days without bleeding/spotting preceded and followed by at least 1 bleeding/spotting day. For Spotting-only episode day(s) with spotting preceded and followed by at least 2 bleeding-free days and for Bleeding/spotting episode Day(s) with bleeding/spotting preceded and followed by at least 2 bleeding-free days.
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End point type |
Secondary
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End point timeframe |
At reference period 4 (1 reference period=90-days) during 1-year treatment phase
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Notes [14] - FAS with evaluable subjects for this outcome |
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No statistical analyses for this end point |
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End point title |
Serum Concentration of Total Levonorgestrel | ||||||||||||||||||
End point description |
Geometric mean and percentage geometric coefficient of variation (%CV) were reported. In the table below, "n" signifies the number of subjects evaluable at the corresponding time points.
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End point type |
Secondary
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End point timeframe |
1, 3, 6, 9, 12 months after insertion
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Notes [15] - FAS |
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No statistical analyses for this end point |
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End point title |
Serum Concentration of Unbound Levonorgestrel | ||||||||||||||||||
End point description |
Geometric mean and (%CV) were reported. In the table below, "n" signifies the number of subjects evaluable at the corresponding time points.
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End point type |
Secondary
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End point timeframe |
1, 3, 6, 9, 12 months after insertion
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Notes [16] - FAS |
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No statistical analyses for this end point |
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End point title |
Serum Concentration of Sex Hormone Binding Globulin (SHBG) | ||||||||
End point description |
The PK of LNG is dependent on SHBG levels as LNG binds specifically to SHBG with high affinity and SHBG synthesis, in turn, is inhibited by LNG.
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End point type |
Secondary
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End point timeframe |
1, 3, 6, 9, 12 months after insertion
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Notes [17] - SHBG needed for calculation of unbound LNG concentration, so data were not summarized and evaluated. |
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No statistical analyses for this end point |
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End point title |
Investigator's Evaluation of Intrauterine System (IUS) Insertion Procedure | ||||||||||||
End point description |
The ease of IUS insertion was evaluated by the investigator as easy, slightly difficult, or very difficult.
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End point type |
Secondary
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End point timeframe |
Month 0
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Notes [18] - FAS with evaluable subjects for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Subjects’ Evaluation of Pain During Intrauterine System (IUS) Insertion Procedure | ||||||||||||||
End point description |
The subject assessed the pain experienced during the insertion as none, mild, moderate or severe and this was recorded by the investigator.
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End point type |
Secondary
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End point timeframe |
Month 0
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Notes [19] - FAS with evaluable subjects for this outcome measure. |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Investigator's Evaluation of Intrauterine System (IUS) Removal Procedure During Treatment Phase | ||||||||||||||
End point description |
The ease of IUS removal was assessed by investigator as easy, slightly difficult or very difficult.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
From start of study treatment until 12 months
|
||||||||||||||
|
|||||||||||||||
Notes [20] - FAS with evaluable subjects for this outcome measure. |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Subject's Evaluation of Pain During Intrauterine System (IUS) Removal Procedure During Treatment Phase | ||||||||||||||
End point description |
The subject assessed the pain experienced during the removal as none, mild, moderate or severe and this was recorded by the investigator.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
From start of treatment up to 12 months
|
||||||||||||||
|
|||||||||||||||
Notes [21] - FAS with evaluable subjects for this outcome measure. |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Investigator's Evaluation of Intrauterine System (IUS) Removal Procedure During Overall Study | ||||||||||||
End point description |
The ease of IUS removal was assessed by investigator as easy, slightly difficult or very difficult.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of study treatment up to 36 months (end of optional extension phase)
|
||||||||||||
|
|||||||||||||
Notes [22] - FAS with evaluable subjects for this outcome measure. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Subject's Evaluation of Pain During Intrauterine System (IUS) Removal Procedure During Overall Study | ||||||||||||||
End point description |
The subject assessed the pain experienced during the removal as none, mild, moderate or severe and this was recorded by the investigator.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
From start of study treatment up to 36 months (end of extension phase)
|
||||||||||||||
|
|||||||||||||||
Notes [23] - FAS with evaluable subjects for this outcome measure. |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Discontinuation Rates by Reason and Year | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The discontinuation rate was calculated from the number of subjects with an expulsion, plus those who had LCS12 removed due to partial expulsion or perforation, plus those who discontinued study treatment for other reasons. The discontinuation rate was classified yearly (Year [Y] 1, Y2 and Y3) for below reasons - Any reason, any adverse event, LCS expulsion, bleeding pattern alterations, increased female genital bleeding, decreased female genital bleeding, and unspecified (unspe) or irregular (irr.) female genital bleeding. In the table below, "n" signifies the number of subjects evaluable at the corresponding time points.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From the start of study treatment until the end of extension phase up to 3 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [24] - FAS |
|||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Discontinuation Rates by Reason | ||||||||||||||||||||||
End point description |
Discontinuation rate was the number and percentage of subjects who discontinued the study drug during the overall period (includes both treatment phase and extension period).
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Up to 36 months
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
Notes [25] - FAS |
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Discontinuation Rates by Reason and Parity During 1 Year Treatment Phase | ||||||||||||||||||||||||
End point description |
Discontinuation rate by reason and parity was the number and percentage of subjects who discontinued the study drug during the 1 year treatment phase.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 12 months
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [26] - FAS |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
From the start of study treatment until the extension phase for up to 3 years
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
|
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Reporting group title |
Levonorgestrel (BAY86-5028)
|
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Reporting group description |
Subjects received levonorgestrel (LNG) intrauterine contraceptive system with an initial in vitro release rate of 12 microgram LNG/day (LCS12) for up to 3 years (the extension phase after 12 months was optional). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
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 autogenerated. Decimal places were automatically truncated if last decimal equals zero. SHBG needed for calculation of unbound LNG concentration, so data were not summarized and evaluated. |