Contraception
Conditions
Keywords
Contraception, Intrauterine, IUD, IUS
Brief summary
This is a study on a new low dose levonorgestrel contraceptive intrauterine systems (LCS). The purpose of the study is to investigate which of the 2 administered doses is the lowest effective intrauterine dose of Levonorgestrel (LNG) administered via the LCS for contraception during 3 years. The study was amended: the LCS16 arm will be extended up to 5 years
Detailed description
Drop out-rate will be covered in Participant flow section.
Interventions
DRUGLCS12
Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 12 microg/24 h
DRUGLCS16
Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 16 microg/24 h
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18 and 35 years (inclusive), in good general health and requesting contraception. * Has regular menstrual cycles (length of cycle 21-35 days) (i.e., endogenous cyclicity without hormonal contraceptive use).
Exclusion criteria
* Known or suspected pregnancy or is lactating. * History of ectopic pregnancies. * Any genital infection (until successfully treated). * Abnormal uterine bleeding of unknown origin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pearl Index up to 3 Years | Up to 3 years | The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 3-year PI was obtained by dividing the number of pregnancies that occurred during the first three years of treatment by the time (in 100 women years) that the women were at risk of getting pregnant. |
| Pearl Index for LCS16 up to 5 Years | Up to 5 years | The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Day 181 to Day 270 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Day 271 to Day 360 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Day 991 to Day 1080 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Day 1 to Day 30 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Day 31 to Day 60 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Classification of Endometrium - Year 1 | At Year 1 | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium |
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Day 61 to Day 90 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Day 91 to Day 120 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Day 331 to Day 360 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Number of Participants With/Without Ovulation - Year 1 | For six weeks in the second half of Year 1 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. |
| Number of Participants With/Without Ovulation - Year 2 | For six weeks in the second half of Year 2 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Day 1 to Day 90 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Classification of Endometrium - Year 2 | At Year 2 | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium |
| Average Total Cervical Score - Year 1 | For six weeks in the second half of Year 1 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) |
| Average Total Cervical Score - Year 2 | For six weeks in the second half of Year 2 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) |
| Average Total Cervical Score - Year 3 | For six weeks in the second half of Year 3 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) |
| Classification of Endometrium - Year 3 / End of Study | At Year 3 / End of study | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium |
| Degree of User Overall Satisfaction With Study Treatment | At the end of study/Year 3 | Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3. |
| Number of Participants With Partial or Total Expulsion | Up to 3 years | If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 | Day 1081 to Day 1170 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 | Day 1711 to Day 1800 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
| Degree of User Overall Satisfaction With Study Treatment up to 5 Years | At the end of study/Year 5 | Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3. |
| Number of Participants With Partial or Total Expulsion up to 5 Years | Up to 5 years | If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion. |
| Number of Participants With/Without Ovulation - Year 3 | For six weeks in the second half of Year 3 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Day 91 to Day 180 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. |
Countries
Argentina, Canada, Chile, Finland, France, Hungary, Mexico, Netherlands, Norway, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LCS12 Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 12 microg/24 h in vitro | 1,432 |
| LCS16 Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 16 microg/24 h in vitro | 1,452 |
| Total | 2,884 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase | Adverse Event | 0 | 36 |
| Extension Phase | Death | 0 | 1 |
| Extension Phase | Lost to Follow-up | 0 | 12 |
| Extension Phase | Other reasons | 0 | 100 |
| Extension Phase | Pregnancy | 0 | 3 |
| Extension Phase | Protocol Violation | 0 | 2 |
| Extension Phase | Withdrawal by Subject | 0 | 3 |
| Treatment up to 3 Years | Adverse Event | 313 | 278 |
| Treatment up to 3 Years | Death | 0 | 1 |
| Treatment up to 3 Years | Lost to Follow-up | 63 | 61 |
| Treatment up to 3 Years | Other reasons | 186 | 186 |
| Treatment up to 3 Years | Pregnancy | 9 | 10 |
| Treatment up to 3 Years | Protocol Violation | 16 | 16 |
| Treatment up to 3 Years | Withdrawal by Subject | 26 | 31 |
Baseline characteristics
| Characteristic | LCS12 | LCS16 | Total |
|---|---|---|---|
| Age, Continuous | 27.2 Years | 27.1 Years | 27.1 Years |
| Age, Customized ≤ 25 years | 566 Participants | 564 Participants | 1130 Participants |
| Age, Customized > 25 years ≤ 35 years | 866 Participants | 888 Participants | 1754 Participants |
| Gender Female | 1432 Participants | 1452 Participants | 2884 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 952 / 1,432 | 1,014 / 1,452 | 1,054 / 1,452 |
| serious Total, serious adverse events | 66 / 1,432 | 72 / 1,452 | 86 / 1,452 |
Outcome results
Primary
Pearl Index for LCS16 up to 5 Years
The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years.
Time frame: Up to 5 years
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCS12 | Pearl Index for LCS16 up to 5 Years | 0.29 Pregnancies per 100 women years |
Comparison: Cumulative failure rate (Kaplan-Meier) at 5 years95% CI: [0.00823, 0.02531]
Primary
Pearl Index up to 3 Years
The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 3-year PI was obtained by dividing the number of pregnancies that occurred during the first three years of treatment by the time (in 100 women years) that the women were at risk of getting pregnant.
Time frame: Up to 3 years
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCS12 | Pearl Index up to 3 Years | 0.33 Pregnancies per 100 women years |
| LCS16 | Pearl Index up to 3 Years | 0.31 Pregnancies per 100 women years |
Comparison: Cumulative failure rate (Kaplan-Meier) at 3 years95% CI: [0.005, 0.017]
Comparison: Cumulative failure rate (Kaplan-Meier) at 3 years95% CI: [0.005, 0.018]
Secondary
Average Total Cervical Score - Year 1
Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
Time frame: For six weeks in the second half of Year 1
Population: A subset of women from the full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCS12 | Average Total Cervical Score - Year 1 | 3.067 Scores on a scale | Standard Deviation 1.291 |
| LCS16 | Average Total Cervical Score - Year 1 | 3.127 Scores on a scale | Standard Deviation 1.62 |
Secondary
Average Total Cervical Score - Year 2
Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
Time frame: For six weeks in the second half of Year 2
Population: A subset of women from the full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCS12 | Average Total Cervical Score - Year 2 | 3.358 Scores on a scale | Standard Deviation 1.272 |
| LCS16 | Average Total Cervical Score - Year 2 | 2.798 Scores on a scale | Standard Deviation 1.499 |
Secondary
Average Total Cervical Score - Year 3
Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
Time frame: For six weeks in the second half of Year 3
Population: A subset of women from the full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCS12 | Average Total Cervical Score - Year 3 | 2.837 Scores on a scale | Standard Deviation 1.354 |
| LCS16 | Average Total Cervical Score - Year 3 | 2.448 Scores on a scale | Standard Deviation 1.521 |
Secondary
Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 1 to Day 30
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of bleeding days | 8.2 Days | Standard Deviation 6 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of spotting only days | 9.7 Days | Standard Deviation 6.5 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of bleeding/spotting days | 18.0 Days | Standard Deviation 8 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of bleeding days | 8.1 Days | Standard Deviation 6.3 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of spotting only days | 9.2 Days | Standard Deviation 6.4 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | Number of bleeding/spotting days | 17.3 Days | Standard Deviation 8 |
Secondary
Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 331 to Day 360
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of bleeding/spotting days | 5.7 Days | Standard Deviation 4.7 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of bleeding days | 2.3 Days | Standard Deviation 2.8 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of spotting only days | 3.4 Days | Standard Deviation 3.4 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of spotting only days | 3.0 Days | Standard Deviation 3.1 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of bleeding/spotting days | 4.6 Days | Standard Deviation 4.4 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | Number of bleeding days | 1.6 Days | Standard Deviation 2.5 |
Secondary
Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 31 to Day 60
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of spotting only days | 7.1 Days | Standard Deviation 5.9 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of bleeding/spotting days | 12.7 Days | Standard Deviation 7.6 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of bleeding days | 5.6 Days | Standard Deviation 4.9 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of bleeding days | 5.5 Days | Standard Deviation 5.3 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of spotting only days | 7.3 Days | Standard Deviation 6.2 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | Number of bleeding/spotting days | 12.9 Days | Standard Deviation 8 |
Secondary
Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 61 to Day 90
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of bleeding/spotting days | 10.3 Days | Standard Deviation 6.9 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of bleeding days | 4.4 Days | Standard Deviation 4.1 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of spotting only days | 5.8 Days | Standard Deviation 5.2 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of bleeding/spotting days | 9.5 Days | Standard Deviation 7 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of bleeding days | 4.1 Days | Standard Deviation 4.5 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | Number of spotting only days | 5.4 Days | Standard Deviation 5.2 |
Secondary
Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 91 to Day 120
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of bleeding/spotting days | 8.6 Days | Standard Deviation 6 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of bleeding days | 3.7 Days | Standard Deviation 3.6 |
| LCS12 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of spotting only days | 4.9 Days | Standard Deviation 4.5 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of bleeding/spotting days | 7.8 Days | Standard Deviation 6.2 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of bleeding days | 3.2 Days | Standard Deviation 3.6 |
| LCS16 | Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | Number of spotting only days | 4.6 Days | Standard Deviation 4.6 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 1 to Day 90
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of bleeding/spotting days | 40.9 Days | Standard Deviation 19.1 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of bleeding days | 18.3 Days | Standard Deviation 12.3 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of spotting only days | 22.6 Days | Standard Deviation 14.1 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of bleeding/spotting days | 39.7 Days | Standard Deviation 19.2 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of bleeding days | 17.7 Days | Standard Deviation 13.2 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | Number of spotting only days | 21.9 Days | Standard Deviation 14 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 991 to Day 1080
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of bleeding days | 4.8 Days | Standard Deviation 5.9 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of spotting only days | 8.6 Days | Standard Deviation 7.1 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of bleeding/spotting days | 13.4 Days | Standard Deviation 9.9 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of bleeding/spotting days | 10.2 Days | Standard Deviation 9.5 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of bleeding days | 3.3 Days | Standard Deviation 5.3 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | Number of spotting only days | 6.9 Days | Standard Deviation 6.8 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 1081 to Day 1170
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 | Number of bleeding days | 3.1 Days | Standard Deviation 4.8 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 | Number of spotting only days | 6.6 Days | Standard Deviation 6.4 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 | Number of bleeding/spotting days | 9.6 Days | Standard Deviation 9 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 91 to Day 180
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of bleeding/spotting days | 23.3 Days | Standard Deviation 14.8 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of bleeding days | 10.2 Days | Standard Deviation 8.7 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of spotting only days | 13.2 Days | Standard Deviation 10.4 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of bleeding/spotting days | 21.1 Days | Standard Deviation 15.1 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of bleeding days | 8.7 Days | Standard Deviation 9.1 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | Number of spotting only days | 12.3 Days | Standard Deviation 10.4 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 1711 to Day 1800
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 | Number of bleeding/spotting days | 9.3 Days | Standard Deviation 8.8 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 | Number of bleeding days | 2.9 Days | Standard Deviation 4.9 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 | Number of spotting only days | 6.4 Days | Standard Deviation 6.1 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 181 to Day 270
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of bleeding/spotting days | 19.4 Days | Standard Deviation 13.2 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of bleeding days | 8.3 Days | Standard Deviation 8.2 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of spotting only days | 11.2 Days | Standard Deviation 9 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of bleeding/spotting days | 16.3 Days | Standard Deviation 12.8 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of bleeding days | 6.3 Days | Standard Deviation 7.5 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | Number of spotting only days | 10.0 Days | Standard Deviation 8.8 |
Secondary
Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4
The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
Time frame: Day 271 to Day 360
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of bleeding/spotting days | 17.6 Days | Standard Deviation 12.1 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of bleeding days | 7.2 Days | Standard Deviation 7.2 |
| LCS12 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of spotting only days | 10.4 Days | Standard Deviation 8.3 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of bleeding/spotting days | 14.3 Days | Standard Deviation 11.8 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of bleeding days | 5.1 Days | Standard Deviation 6.6 |
| LCS16 | Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | Number of spotting only days | 9.1 Days | Standard Deviation 8.2 |
Secondary
Classification of Endometrium - Year 1
The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
Time frame: At Year 1
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Classification of Endometrium - Year 1 | Unclassified | 1 Participants |
| LCS12 | Classification of Endometrium - Year 1 | Atrophic/inactive | 0 Participants |
| LCS12 | Classification of Endometrium - Year 1 | Proliferative | 0 Participants |
| LCS12 | Classification of Endometrium - Year 1 | Secretory | 25 Participants |
| LCS12 | Classification of Endometrium - Year 1 | Menstrual | 0 Participants |
| LCS16 | Classification of Endometrium - Year 1 | Menstrual | 0 Participants |
| LCS16 | Classification of Endometrium - Year 1 | Secretory | 22 Participants |
| LCS16 | Classification of Endometrium - Year 1 | Atrophic/inactive | 0 Participants |
| LCS16 | Classification of Endometrium - Year 1 | Unclassified | 1 Participants |
| LCS16 | Classification of Endometrium - Year 1 | Proliferative | 0 Participants |
Secondary
Classification of Endometrium - Year 2
The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
Time frame: At Year 2
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Classification of Endometrium - Year 2 | Proliferative | 0 Participants |
| LCS12 | Classification of Endometrium - Year 2 | Menstrual | 0 Participants |
| LCS12 | Classification of Endometrium - Year 2 | Secretory | 19 Participants |
| LCS12 | Classification of Endometrium - Year 2 | Unclassified | 3 Participants |
| LCS12 | Classification of Endometrium - Year 2 | Atrophic/inactive | 0 Participants |
| LCS16 | Classification of Endometrium - Year 2 | Unclassified | 0 Participants |
| LCS16 | Classification of Endometrium - Year 2 | Atrophic/inactive | 0 Participants |
| LCS16 | Classification of Endometrium - Year 2 | Proliferative | 0 Participants |
| LCS16 | Classification of Endometrium - Year 2 | Secretory | 19 Participants |
| LCS16 | Classification of Endometrium - Year 2 | Menstrual | 0 Participants |
Secondary
Classification of Endometrium - Year 3 / End of Study
The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
Time frame: At Year 3 / End of study
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Classification of Endometrium - Year 3 / End of Study | Unclassified | 1 Participants |
| LCS12 | Classification of Endometrium - Year 3 / End of Study | Proliferative | 0 Participants |
| LCS12 | Classification of Endometrium - Year 3 / End of Study | Atrophic/inactive | 0 Participants |
| LCS12 | Classification of Endometrium - Year 3 / End of Study | Secretory | 24 Participants |
| LCS12 | Classification of Endometrium - Year 3 / End of Study | Menstrual | 0 Participants |
| LCS16 | Classification of Endometrium - Year 3 / End of Study | Secretory | 22 Participants |
| LCS16 | Classification of Endometrium - Year 3 / End of Study | Menstrual | 0 Participants |
| LCS16 | Classification of Endometrium - Year 3 / End of Study | Unclassified | 0 Participants |
| LCS16 | Classification of Endometrium - Year 3 / End of Study | Atrophic/inactive | 0 Participants |
| LCS16 | Classification of Endometrium - Year 3 / End of Study | Proliferative | 1 Participants |
Secondary
Degree of User Overall Satisfaction With Study Treatment
Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3.
Time frame: At the end of study/Year 3
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Missing | 1 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Very satisfied | 796 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Somewhat satisfied | 201 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Neither satisfied / dissatisfied | 31 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Dissatisfied | 23 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment | Very dissatisfied | 1 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Dissatisfied | 18 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Missing | 1 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Neither satisfied / dissatisfied | 22 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Somewhat satisfied | 177 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Very satisfied | 842 Participants |
| LCS16 | Degree of User Overall Satisfaction With Study Treatment | Very dissatisfied | 3 Participants |
Secondary
Degree of User Overall Satisfaction With Study Treatment up to 5 Years
Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3.
Time frame: At the end of study/Year 5
Population: All participants from the full analysis set who participated in the extension phase and had an assessment for this evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Very satisfied | 610 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Somewhat satisfied | 70 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Neither satisfied / dissatisfied | 3 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Dissatisfied | 1 Participants |
| LCS12 | Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Very dissatisfied | 2 Participants |
Secondary
Number of Participants With Partial or Total Expulsion
If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion.
Time frame: Up to 3 years
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Number of Participants With Partial or Total Expulsion | IUS partially expelled | 24 Participants |
| LCS12 | Number of Participants With Partial or Total Expulsion | IUS totally expelled | 29 Participants |
| LCS16 | Number of Participants With Partial or Total Expulsion | IUS partially expelled | 30 Participants |
| LCS16 | Number of Participants With Partial or Total Expulsion | IUS totally expelled | 16 Participants |
Secondary
Number of Participants With Partial or Total Expulsion up to 5 Years
If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion.
Time frame: Up to 5 years
Population: All participants from the full analysis set who had an assessment for this evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Number of Participants With Partial or Total Expulsion up to 5 Years | IUS partially expelled | 35 Participants |
| LCS12 | Number of Participants With Partial or Total Expulsion up to 5 Years | IUS totally expelled | 19 Participants |
Secondary
Number of Participants With/Without Ovulation - Year 1
Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
Time frame: For six weeks in the second half of Year 1
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Number of Participants With/Without Ovulation - Year 1 | With ovulation | 13 Participants |
| LCS12 | Number of Participants With/Without Ovulation - Year 1 | Without ovulation | 1 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 1 | With ovulation | 11 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 1 | Without ovulation | 1 Participants |
Secondary
Number of Participants With/Without Ovulation - Year 2
Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
Time frame: For six weeks in the second half of Year 2
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Number of Participants With/Without Ovulation - Year 2 | With ovulation | 10 Participants |
| LCS12 | Number of Participants With/Without Ovulation - Year 2 | Without ovulation | 1 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 2 | With ovulation | 9 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 2 | Without ovulation | 1 Participants |
Secondary
Number of Participants With/Without Ovulation - Year 3
Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
Time frame: For six weeks in the second half of Year 3
Population: A subset of women from the full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCS12 | Number of Participants With/Without Ovulation - Year 3 | Without ovulation | 0 Participants |
| LCS12 | Number of Participants With/Without Ovulation - Year 3 | With ovulation | 11 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 3 | Without ovulation | 0 Participants |
| LCS16 | Number of Participants With/Without Ovulation - Year 3 | With ovulation | 7 Participants |