Contraception
Conditions
Keywords
contraception, intrauterine, long-term, reversible
Brief summary
The primary objective of this study is to assess the efficacy of a levonorgestrel-releasing intrauterine system (LNG20) in nulliparous and parous females of child-bearing potential who request long-term, reversible contraception for up to 10 years.
Detailed description
This is a Phase 3, randomized, open-label, multicenter evaluation of the efficacy of a levonorgestrel-releasing intrauterine system (LNG20). The goals of the study include provision of information to understand efficacy and safety within the widest range of possible users of the LNG20. Typically, intrauterine contraceptive studies only include women 18-35 years of age for efficacy and safety, and place limits on parity and larger body size. Women outside of these characteristics also desire an effective intrauterine contraceptive. Accordingly, this study will include women who are both nulliparous and parous as well as women less than 18 years of age in the primary efficacy and safety analyses
Interventions
DRUGLNG20
levonorgestrel-releasing intrauterine system for contraception
DRUGMirena
Mirena intrauterine system
Sponsors
Medicines360
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy women requesting contraception * 16-35 years old * Cohort 36-45 years old * Sexually active
Exclusion criteria
* Currently pregnant, pregnant within 4 weeks prior to study entry or planning pregnancy within 24 months of study entry * Currently breastfeeding * Current persistent, abnormal vaginal bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Pregnancies Per Year | 10 years | Number of pregnancies per year in each treatment arm. |
| Cumulative Pearl Index | 8 years | The Pearl Index (PI) is an estimate of the number of pregnancies per 100 women-years of contraceptive exposure. The Pearl Index is calculated as the number of on treatment pregnancies in the study divided by the total number of complete 28-day cycles of use in the study multiplied by 1,300 (13 cycles/yr x 100 years). Cycles where other birth control methods were used were excluded from this measure. The Pearl Index for MIRENA was not a pre-specified primary outcome measure and is therefore not included. There is only 8 years of data due to the early termination of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuation Rates | 10 Years | The rate of continuation of usage over time. |
| Return of Menses After Discontinuation | 5 months | Subjects who discontinued from the trial and who were not pregnant or did not start a hormonal contraceptive were followed to assess the return of menses after IUS removal. If after three months menses had not occurred, the subject was to be evaluated for the cause of their secondary amenorrhea and continued to be followed monthly until the diagnosis was established. |
| Return to Fertility After Discontinuation | 12 months | Subjects who discontinued from the trial and desired pregnancy were followed for up to 12 months to assess fertility after IUS removal. |
| Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | 5 Years | The Mean Plasma Pharmacokinetics of LNG in a Subset of Subjects through 60 Months of Use. Non-obese was defined as a BMI less than 30 kg/m\^2. Obese was defined as a BMI of 30 kg/m\^2 or higher. |
| Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | month 36 through 120 | The Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120. |
| Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years | 10 Years | The Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years. |
| Safety and Tolerability | 10 Years | The safety and tolerability based on the report of adverse events and serious adverse events |
| Incidence of Bleeding and/or Spotting | 8 Years | From data based on the daily diary log, number of IUS subjects experiencing some bleeding and/or spotting. |
| Cumulative Pregnancy Rates | 8 years | Life table methods were used to estimate the cumulative pregnancy rate after each year. Confirmed pregnancy was the failure outcome and the corresponding time to pregnancy was the failure time. Time to pregnancy was calculated as the date a confirmed pregnancy was initially reported minus the date of IUS placement plus one. |
| Expulsion Rate | 10 years | The expulsion rate includes the number of subjects with reported expulsions or removal of the IUS, regardless of reason. |
| Change in Hemoglobin Values | 10 years | Measuring the change in hemoglobin results from the screening visit and following 12 months, 60 months and 120 months of product use. |
| Discontinuation for Safety Reasons | 10 years | Time to event was calculated as the date of continuation/expulsion/removal minus the date of IUS placement plus one. Subjects without a continuation/expulsion/removal were censored at the last contact date and failure time was calculated as the last contact date minus the date of IUS placement plus one. |
| Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | 8 Years | Analysis of residual LNG content from an appropriate sampling of IUSs that were removed or expelled during the study was to be summarized and plotted as a function of time of removal/expulsion. Residual drug content analysis was performed on a sampling of removed or expelled samples to determine the average in vivo drug release rate during the time the samples were implanted. All available samples were sorted and grouped by duration of use in 90-day intervals. The drug content and time of exposure of the samples analyzed were fit by an exponential regression to calculate the initial and average in vivo release rate over the duration of the study. NOTE: Year = 360 day intervals |
| Distribution of Bleeding Amenorrhea by 90 Day Interval | 8 Years | The incidence of diary reported bleeding and/or spotting by 90-day interval, as an assessment of IUS-induced amenorrhea, is summarized as the number of subjects reporting no bleeding and/or spotting. |
Countries
United States
Participant flow
Pre-assignment details
Enrollment into the Mirena arm was stopped when it was determined that sufficient comparative safety data for LILETTA vs. Mirena was already available; thereafter, subjects were only assigned to LILETTA. The data cutoff date of 05 April 2021 was chosen for all LILETTA subjects as it coincides with all subjects completing through Year 8 of use (intended duration of use for the product). All Mirena participants were discontinued by the end of Year 5.
Participants by arm
| Arm | Count |
|---|---|
| LNG20 (16-35 Yr Olds) LNG20 levonorgestrel-releasing intrauterine system LNG20: levonorgestrel-releasing intrauterine system for contraception sub-population (16-35 years old) | 1,600 |
| Mirena Levonorgestrel-releasing intrauterine system for contraception
Mirena: Mirena intrauterine system | 159 |
| LNG20 (36-45 Yr Olds) LNG20 levonorgestrel-releasing intrauterine system LNG20: levonorgestrel-releasing intrauterine system for contraception sub-population (36-45 years old) | 151 |
| Total | 1,910 |
Baseline characteristics
| Characteristic | LNG20 (16-35 Yr Olds) | Total | LNG20 (36-45 Yr Olds) | Mirena |
|---|---|---|---|---|
| Age, Customized Age 16-35 years | 1,600 Participants | 1759 Participants | 0 Participants | 159 Participants |
| Age, Customized Age 36-45 years | 0 Participants | 151 Participants | 151 Participants | 0 Participants |
| Age, Customized | 26.2 years STANDARD_DEVIATION 4.4 | 27.2 years STANDARD_DEVIATION 5.6 | 39.6 years STANDARD_DEVIATION 2.7 | 26.1 years STANDARD_DEVIATION 4.4 |
| BMI BMI ≤24.9 | 823 Participants | 950 Participants | 59 Participants | 68 Participants |
| BMI BMI 25-29.9 | 390 Participants | 479 Participants | 37 Participants | 52 Participants |
| BMI BMI 30-39.9 | 304 Participants | 373 Participants | 41 Participants | 28 Participants |
| BMI BMI ≥40 | 79 Participants | 104 Participants | 14 Participants | 11 Participants |
| BMI No Weight Taken at Baseline | 4 Participants | 4 Participants | 0 Participants | 0 Participants |
| BMI | 26.8 (kg/m^2) STANDARD_DEVIATION 6.7 | 26.9 (kg/m^2) STANDARD_DEVIATION 6.8 | 28.6 (kg/m^2) STANDARD_DEVIATION 7.6 | 27.2 (kg/m^2) STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 237 Participants | 279 Participants | 21 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1363 Participants | 1631 Participants | 130 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Parity Nulliparous | 989 Participants | 1101 Participants | 22 Participants | 90 Participants |
| Parity Parous | 611 Participants | 809 Participants | 129 Participants | 69 Participants |
| Partner Status Does Not Live with Partner | 685 Participants | 805 Participants | 45 Participants | 75 Participants |
| Partner Status Lives with Partner | 915 Participants | 1105 Participants | 106 Participants | 84 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 19 Participants | 23 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 73 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 212 Participants | 244 Participants | 20 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 49 Participants | 58 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 6 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1250 Participants | 1501 Participants | 120 Participants | 131 Participants |
| Sex: Female, Male Female | 1600 Participants | 1910 Participants | 151 Participants | 159 Participants |
| Sex: Female, Male Male | 0 Participants | 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 | 1 / 1,600 | 0 / 159 | 0 / 151 |
| other Total, other adverse events | 1,441 / 1,600 | 138 / 159 | 137 / 151 |
| serious Total, serious adverse events | 78 / 1,600 | 6 / 159 | 8 / 151 |
Outcome results
Primary
Cumulative Pearl Index
The Pearl Index (PI) is an estimate of the number of pregnancies per 100 women-years of contraceptive exposure. The Pearl Index is calculated as the number of on treatment pregnancies in the study divided by the total number of complete 28-day cycles of use in the study multiplied by 1,300 (13 cycles/yr x 100 years). Cycles where other birth control methods were used were excluded from this measure. The Pearl Index for MIRENA was not a pre-specified primary outcome measure and is therefore not included. There is only 8 years of data due to the early termination of the study.
Time frame: 8 years
Population: The Pearl Index for MIRENA was not a pre-specified primary outcome measure and is therefore not included. The number of participants analyzed for this measure is the MITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 1 | 0.15 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 2 | 0.25 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 3 | 0.21 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 4 | 0.20 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 5 | 0.19 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 6 | 0.17 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 7 | 0.19 pregnancies per 100 women-years |
| LNG20 (16-35 Yr Olds) | Cumulative Pearl Index | Year 8 | 0.19 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 8 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 1 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 5 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 2 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 7 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 3 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 6 | 0.0 pregnancies per 100 women-years |
| Mirena | Cumulative Pearl Index | Year 4 | 0.0 pregnancies per 100 women-years |
Primary
Number of Pregnancies Per Year
Number of pregnancies per year in each treatment arm.
Time frame: 10 years
Population: All Mirena participants were discontinued by end of Year 5; therefore, Years 6-10 are considered not available for that arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 5 | 1 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 6 | 0 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 7 | 2 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 8 | 0 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 9 | 0 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 4 | 1 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 1 | 2 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 2 | 4 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 3 | 1 pregnancies |
| LNG20 (16-35 Yr Olds) | Number of Pregnancies Per Year | Year 10 | 0 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 3 | 0 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 5 | 1 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 4 | 0 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 9 | NA pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 6 | NA pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 10 | NA pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 2 | 0 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 7 | NA pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 1 | 1 pregnancies |
| Mirena | Number of Pregnancies Per Year | Year 8 | NA pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 7 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 8 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 3 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 4 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 9 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 1 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 5 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 10 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 6 | 0 pregnancies |
| LNG20 (36-45 Yr Olds) | Number of Pregnancies Per Year | Year 2 | 0 pregnancies |
Secondary
Change in Hemoglobin Values
Measuring the change in hemoglobin results from the screening visit and following 12 months, 60 months and 120 months of product use.
Time frame: 10 years
Population: No standard deviation since there was only one Mirena participant measured at month 120
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 60 | 0.3 g/dL | Standard Deviation 1 |
| LNG20 (16-35 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 12 | 0.2 g/dL | Standard Deviation 0.9 |
| LNG20 (16-35 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 120 | 0.3 g/dL | Standard Deviation 1 |
| Mirena | Change in Hemoglobin Values | Change from Screening to Month 60 | 0.1 g/dL | Standard Deviation 1.1 |
| Mirena | Change in Hemoglobin Values | Change from Screening to Month 12 | 0.2 g/dL | Standard Deviation 1.1 |
| Mirena | Change in Hemoglobin Values | Change from Screening to Month 120 | -0.7 g/dL | — |
| LNG20 (36-45 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 12 | 0.1 g/dL | Standard Deviation 0.8 |
| LNG20 (36-45 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 120 | 0.3 g/dL | Standard Deviation 0.9 |
| LNG20 (36-45 Yr Olds) | Change in Hemoglobin Values | Change from Screening to Month 60 | 0.3 g/dL | Standard Deviation 0.8 |
Secondary
Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years
The Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years.
Time frame: 10 Years
Population: Endometrial thickness (ET) was evaluated in 52 LILETTA Efficacy Group subjects in the LNG20 (16-35 Yr Olds) arm only, with data both at Baseline and Month 12 (ET population) as part of a substudy conducted within the main protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years | Baseline | 4.0 Endometrial Thickness (mm) | Standard Deviation 2.4 |
| LNG20 (16-35 Yr Olds) | Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years | Month 12 | 3.8 Endometrial Thickness (mm) | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years | Month 60 | 3.1 Endometrial Thickness (mm) | Standard Deviation 1.5 |
| LNG20 (16-35 Yr Olds) | Changes in Endometrial Thickness Based on Transvaginal Ultrasonography at One Year, Five Years and Ten Years | Month 120 | 2.6 Endometrial Thickness (mm) | Standard Deviation 1.1 |
Secondary
Continuation Rates
The rate of continuation of usage over time.
Time frame: 10 Years
Population: All Mirena participants were discontinued by the end of Year 5 per the study protocol. All LNG20 (36-45 Yr Old) participants were discontinued by the end of Year 8 per the study protocol. Month 6 is defined as 182 days of use, Year 1= 365 days, Year 2= 730 days, Year 3= 1095 days, Year 4= 1460 days, Year 5= 1825 days, Year 6= 2190 days, Year 7= 2555 days, Year 8= 2920 days, Year 9= 3285 days, and Year 10= 3650 days of product use.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Month 6 Through Year 1 | 1275 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 6 Through Year 7 | 402 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 3 Through Year 4 | 720 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Through Month 6 | 1420 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 5 Through Year 6 | 498 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 4 Through Year 5 | 597 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 8 Through Year 9 | 83 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 1 Through Year 2 | 1034 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 9 Through Year 10 | 76 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 7 Through Year 8 | 293 Participants |
| LNG20 (16-35 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 2 Through Year 3 | 859 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 6 Through Year 7 | 0 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Through Month 6 | 131 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Month 6 Through Year 1 | 118 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 1 Through Year 2 | 86 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 2 Through Year 3 | 64 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 3 Through Year 4 | 49 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 4 Through Year 5 | 21 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 5 Through Year 6 | 0 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 7 Through Year 8 | 0 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 8 Through Year 9 | 0 Participants |
| Mirena | Continuation Rates | Number of Subjects Continuing Year 9 Through Year 10 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 2 Through Year 3 | 105 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 6 Through Year 7 | 72 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 1 Through Year 2 | 114 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Through Month 6 | 133 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 7 Through Year 8 | 39 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Month 6 Through Year 1 | 125 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 9 Through Year 10 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 4 Through Year 5 | 91 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 3 Through Year 4 | 98 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 8 Through Year 9 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Continuation Rates | Number of Subjects Continuing Year 5 Through Year 6 | 77 Participants |
Secondary
Cumulative Pregnancy Rates
Life table methods were used to estimate the cumulative pregnancy rate after each year. Confirmed pregnancy was the failure outcome and the corresponding time to pregnancy was the failure time. Time to pregnancy was calculated as the date a confirmed pregnancy was initially reported minus the date of IUS placement plus one.
Time frame: 8 years
Population: Note: a year is considered 364 days (13 women-months). Only the efficacy population (LNG20 16-35 years old) was evaluated, per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 1 | 0.14 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 2 | 0.49 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 3 | 0.59 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 4 | 0.72 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 5 | 0.87 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 6 | 0.87 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 7 | 1.30 number of pregnancies per year |
| LNG20 (16-35 Yr Olds) | Cumulative Pregnancy Rates | Year 8 | 1.30 number of pregnancies per year |
Secondary
Discontinuation for Safety Reasons
Time to event was calculated as the date of continuation/expulsion/removal minus the date of IUS placement plus one. Subjects without a continuation/expulsion/removal were censored at the last contact date and failure time was calculated as the last contact date minus the date of IUS placement plus one.
Time frame: 10 years
Population: All Mirena participants were discontinued by end of Year 5 per the study protocol. All LNG20 (36-45 Yr Old) participants were discontinued by Year 8 per the study protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 7 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 3 | 1 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 8 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 9 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 10 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 1 | 5 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 4 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 2 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 5 | 0 Participants |
| LNG20 (16-35 Yr Olds) | Discontinuation for Safety Reasons | Year 6 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 7 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 4 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 6 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 8 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 3 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 1 | 3 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 9 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 5 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 10 | 0 Participants |
| Mirena | Discontinuation for Safety Reasons | Year 2 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 10 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 1 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 2 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 3 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 4 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 5 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 6 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 7 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 8 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Discontinuation for Safety Reasons | Year 9 | 0 Participants |
Secondary
Distribution of Bleeding Amenorrhea by 90 Day Interval
The incidence of diary reported bleeding and/or spotting by 90-day interval, as an assessment of IUS-induced amenorrhea, is summarized as the number of subjects reporting no bleeding and/or spotting.
Time frame: 8 Years
Population: All Mirena participants were discontinued by end of Year 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 32 (Month 96) | 115 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 20 (Month 60) | 249 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 12 (Month 36) | 319 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 1 (Month 3) | 6 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 16 (Month 48) | 275 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 28 (Month 84) | 157 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 4 (Month 12) | 250 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 2 (Month 6) | 167 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 24 (Month 72) | 199 Participants |
| LNG20 (16-35 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 8 (Month 24) | 283 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 12 (Month 36) | 21 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 1 (Month 3) | 0 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 2 (Month 6) | 27 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 4 (Month 12) | 26 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 8 (Month 24) | 27 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 16 (Month 48) | 23 Participants |
| Mirena | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 20 (Month 60) | 16 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 16 (Month 48) | 37 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 8 (Month 24) | 35 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 32 (Month 96) | 28 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 20 (Month 60) | 35 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 4 (Month 12) | 19 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 24 (Month 72) | 33 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 2 (Month 6) | 16 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 28 (Month 84) | 33 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 12 (Month 36) | 40 Participants |
| LNG20 (36-45 Yr Olds) | Distribution of Bleeding Amenorrhea by 90 Day Interval | 90 Day Interval 1 (Month 3) | 1 Participants |
Secondary
Expulsion Rate
The expulsion rate includes the number of subjects with reported expulsions or removal of the IUS, regardless of reason.
Time frame: 10 years
Population: All Mirena participants were discontinued by end of Year 5 per the study protocol. All LNG20 (36-45 Yr Old) participants were discontinued by end of Year 8 per the study protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Expulsion Rate | IUS Placement through Year 1 | 47 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 1 through Year 2 | 5 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 2 through Year 3 | 2 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 3 through Year 4 | 2 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 4 through Year 5 | 1 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 5 through Year 6 | 2 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 6 through Year 7 | 2 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 7 through Year 8 | 2 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 8 through Year 9 | 1 Participants |
| LNG20 (16-35 Yr Olds) | Expulsion Rate | Year 9 through Year 10 | 0 Participants |
| Mirena | Expulsion Rate | Year 8 through Year 9 | 0 Participants |
| Mirena | Expulsion Rate | IUS Placement through Year 1 | 8 Participants |
| Mirena | Expulsion Rate | Year 5 through Year 6 | 0 Participants |
| Mirena | Expulsion Rate | Year 4 through Year 5 | 0 Participants |
| Mirena | Expulsion Rate | Year 1 through Year 2 | 4 Participants |
| Mirena | Expulsion Rate | Year 9 through Year 10 | 0 Participants |
| Mirena | Expulsion Rate | Year 7 through Year 8 | 0 Participants |
| Mirena | Expulsion Rate | Year 2 through Year 3 | 0 Participants |
| Mirena | Expulsion Rate | Year 6 through Year 7 | 0 Participants |
| Mirena | Expulsion Rate | Year 3 through Year 4 | 1 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 7 through Year 8 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 3 through Year 4 | 2 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 4 through Year 5 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 5 through Year 6 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 8 through Year 9 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 6 through Year 7 | 1 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | IUS Placement through Year 1 | 3 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 9 through Year 10 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 1 through Year 2 | 1 Participants |
| LNG20 (36-45 Yr Olds) | Expulsion Rate | Year 2 through Year 3 | 0 Participants |
Secondary
Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study
Analysis of residual LNG content from an appropriate sampling of IUSs that were removed or expelled during the study was to be summarized and plotted as a function of time of removal/expulsion. Residual drug content analysis was performed on a sampling of removed or expelled samples to determine the average in vivo drug release rate during the time the samples were implanted. All available samples were sorted and grouped by duration of use in 90-day intervals. The drug content and time of exposure of the samples analyzed were fit by an exponential regression to calculate the initial and average in vivo release rate over the duration of the study. NOTE: Year = 360 day intervals
Time frame: 8 Years
Population: In this substudy, a sampling of removed or expelled LNG20 IUSs were evaluated for residual drug content from Day 1 through Year 8. The total number of IUSs analyzed was 130 units from a total of 130 participants. All IUSs came from participants in the LNG20 (16-35 Yr Olds) arm. IUSs from participants in the Mirena arm were not evaluated in this substudy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 1 | 45.1 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 2 | 39.1 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 3 | 33.8 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 4 | 29.3 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 5 | 25.4 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 6 | 22.0 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 7 | 19.1 mg/day | Standard Deviation 1.8 |
| LNG20 (16-35 Yr Olds) | Ex Vivo Analysis of IUSs That Are Removed or Expelled During the Study | Year 8 | 16.6 mg/day | Standard Deviation 1.8 |
Secondary
Incidence of Bleeding and/or Spotting
From data based on the daily diary log, number of IUS subjects experiencing some bleeding and/or spotting.
Time frame: 8 Years
Population: Any incidences of bleeding and/or spotting were self-reported via daily diary log by remaining participants at regular intervals throughout the length of the study. All Mirena participants were discontinued by the end of Year 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 5 | 369 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 2 | 779 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 2 (Days 29 - 57) | 1394 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 4 | 468 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 3 | 557 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 1 (Days 0- 28) | 1536 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 7 | 260 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 3 (Days 58 - 86) | 1276 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 8 | 189 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 6 | 310 Participants |
| LNG20 (16-35 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 1 | 1070 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Year 1 | 97 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Cycle 1 (Days 0- 28) | 150 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Cycle 2 (Days 29 - 57) | 131 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Cycle 3 (Days 58 - 86) | 122 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Year 2 | 54 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Year 3 | 44 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Year 4 | 28 Participants |
| Mirena | Incidence of Bleeding and/or Spotting | Year 5 | 22 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 1 (Days 0- 28) | 145 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 4 | 60 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 1 | 109 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 8 | 33 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 5 | 54 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 3 (Days 58 - 86) | 122 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 6 | 45 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Cycle 2 (Days 29 - 57) | 139 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 7 | 39 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 3 | 65 Participants |
| LNG20 (36-45 Yr Olds) | Incidence of Bleeding and/or Spotting | Year 2 | 79 Participants |
Secondary
Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy
The Mean Plasma Pharmacokinetics of LNG in a Subset of Subjects through 60 Months of Use. Non-obese was defined as a BMI less than 30 kg/m\^2. Obese was defined as a BMI of 30 kg/m\^2 or higher.
Time frame: 5 Years
Population: Mean Plasma Levonorgestrel Concentrations (pg/mL) for All Subjects in the PK Substudy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 9 | 134.9 (pg/mL) | Standard Deviation 38.4 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 1 | 180.5 (pg/mL) | Standard Deviation 44.8 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 36 | 104 (pg/mL) | Standard Deviation 53.9 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 12 | 140.5 (pg/mL) | Standard Deviation 52.6 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 2 | 199.3 (pg/mL) | Standard Deviation 59 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 30 | 111.1 (pg/mL) | Standard Deviation 33.2 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 18 | 126.3 (pg/mL) | Standard Deviation 32.6 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 48 | 93.2 (pg/mL) | Standard Deviation 30.6 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 24 | 115.7 (pg/mL) | Standard Deviation 26.6 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 3 | 166.8 (pg/mL) | Standard Deviation 40.8 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 60 | 68.1 (pg/mL) | Standard Deviation 30.3 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 1 | 187.6 (pg/mL) | Standard Deviation 53.4 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 6 | 153.7 (pg/mL) | Standard Deviation 40 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 54 | 93.7 (pg/mL) | Standard Deviation 22.3 |
| LNG20 (16-35 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 42 | 101.7 (pg/mL) | Standard Deviation 43.9 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 42 | 131 (pg/mL) | Standard Deviation 51 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 1 | 328.9 (pg/mL) | Standard Deviation 150 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 2 | 320.3 (pg/mL) | Standard Deviation 147.4 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 1 | 251 (pg/mL) | Standard Deviation 98.2 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 3 | 222.7 (pg/mL) | Standard Deviation 58.5 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 6 | 215.8 (pg/mL) | Standard Deviation 59 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 9 | 184.9 (pg/mL) | Standard Deviation 52.4 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 12 | 182.5 (pg/mL) | Standard Deviation 43.9 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 18 | 168.1 (pg/mL) | Standard Deviation 32.1 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 24 | 150.2 (pg/mL) | Standard Deviation 28.9 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 30 | 161.1 (pg/mL) | Standard Deviation 51.3 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 36 | 152.3 (pg/mL) | Standard Deviation 50.5 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 48 | 114.5 (pg/mL) | Standard Deviation 33.8 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 54 | 103.3 (pg/mL) | Standard Deviation 43.5 |
| Mirena | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 60 | 136.9 (pg/mL) | Standard Deviation 62.4 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 9 | 229.9 (pg/mL) | Standard Deviation 69.9 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 54 | 127.3 (pg/mL) | Standard Deviation 40.8 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 36 | 152.6 (pg/mL) | Standard Deviation 38.4 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 6 | 229.5 (pg/mL) | Standard Deviation 67.3 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 3 | 237.4 (pg/mL) | Standard Deviation 75 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 42 | 151.9 (pg/mL) | Standard Deviation 41.8 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 1 | 247.7 (pg/mL) | Standard Deviation 82.6 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 1 | 310 (pg/mL) | Standard Deviation 139.7 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 48 | 136.1 (pg/mL) | Standard Deviation 37.9 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 18 | 168.6 (pg/mL) | Standard Deviation 38.5 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Week 2 | 278.7 (pg/mL) | Standard Deviation 107 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 24 | 180.8 (pg/mL) | Standard Deviation 39.9 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 12 | 192.3 (pg/mL) | Standard Deviation 36.2 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 60 | 109.5 (pg/mL) | Standard Deviation 34.9 |
| LNG20 (36-45 Yr Olds) | Mean Plasma Levonorgestrel Concentrations (pg/mL) for Subjects in the PK Substudy | Month 30 | 164.2 (pg/mL) | Standard Deviation 43.5 |
Secondary
Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120
The Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120.
Time frame: month 36 through 120
Population: Plasma Levonorgestrel Concentrations for All Subjects Beginning at Month 36. All Mirena participants were discontinued by the end of Year 5.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 36 | 129.879 Levonorgestrel Concentration (pg/mL) | Standard Deviation 49.793 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 42 | 117.907 Levonorgestrel Concentration (pg/mL) | Standard Deviation 46.533 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 48 | 110.109 Levonorgestrel Concentration (pg/mL) | Standard Deviation 47.046 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 54 | 105.095 Levonorgestrel Concentration (pg/mL) | Standard Deviation 43.37 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 60 | 97.721 Levonorgestrel Concentration (pg/mL) | Standard Deviation 38.819 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 66 | 94.284 Levonorgestrel Concentration (pg/mL) | Standard Deviation 34.73 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 72 | 89.805 Levonorgestrel Concentration (pg/mL) | Standard Deviation 42.318 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 78 | 87.897 Levonorgestrel Concentration (pg/mL) | Standard Deviation 32.714 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 84 | 91.179 Levonorgestrel Concentration (pg/mL) | Standard Deviation 38.381 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 90 | 84.206 Levonorgestrel Concentration (pg/mL) | Standard Deviation 31.74 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 96 | 83.425 Levonorgestrel Concentration (pg/mL) | Standard Deviation 34.159 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 108 | 79.499 Levonorgestrel Concentration (pg/mL) | Standard Deviation 36.386 |
| LNG20 (16-35 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 120 | 88.308 Levonorgestrel Concentration (pg/mL) | Standard Deviation 41.251 |
| Mirena | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 36 | 141.175 Levonorgestrel Concentration (pg/mL) | Standard Deviation 60.438 |
| Mirena | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 42 | 142.036 Levonorgestrel Concentration (pg/mL) | Standard Deviation 73.278 |
| Mirena | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 54 | 113.836 Levonorgestrel Concentration (pg/mL) | Standard Deviation 40.715 |
| Mirena | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 48 | 136.894 Levonorgestrel Concentration (pg/mL) | Standard Deviation 97.898 |
| Mirena | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 60 | 111.676 Levonorgestrel Concentration (pg/mL) | Standard Deviation 49.42 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 84 | 87.673 Levonorgestrel Concentration (pg/mL) | Standard Deviation 37.769 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 42 | 155.518 Levonorgestrel Concentration (pg/mL) | Standard Deviation 96.174 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 72 | 98.542 Levonorgestrel Concentration (pg/mL) | Standard Deviation 47.527 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 48 | 141.066 Levonorgestrel Concentration (pg/mL) | Standard Deviation 73.341 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 96 | 98.767 Levonorgestrel Concentration (pg/mL) | Standard Deviation 39.647 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 54 | 140.576 Levonorgestrel Concentration (pg/mL) | Standard Deviation 81.446 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 78 | 84.353 Levonorgestrel Concentration (pg/mL) | Standard Deviation 39.021 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 60 | 118.826 Levonorgestrel Concentration (pg/mL) | Standard Deviation 55.593 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 90 | 97.65 Levonorgestrel Concentration (pg/mL) | Standard Deviation 38.203 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 66 | 102.41 Levonorgestrel Concentration (pg/mL) | Standard Deviation 43.507 |
| LNG20 (36-45 Yr Olds) | Plasma LNG Levels in All Subjects With Continuing Use From Month 36 Through Month 120 | Month 36 | 152.693 Levonorgestrel Concentration (pg/mL) | Standard Deviation 76.452 |
Secondary
Return of Menses After Discontinuation
Subjects who discontinued from the trial and who were not pregnant or did not start a hormonal contraceptive were followed to assess the return of menses after IUS removal. If after three months menses had not occurred, the subject was to be evaluated for the cause of their secondary amenorrhea and continued to be followed monthly until the diagnosis was established.
Time frame: 5 months
Population: Only those subjects who completed this evaluation are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Number (%) of Subjects With Onset of Menses Post-IUS Removal | 651 Participants |
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Month 1 | 492 Participants |
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Month 2 | 141 Participants |
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Month 3 | 15 Participants |
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Month 4 | 1 Participants |
| LNG20 (16-35 Yr Olds) | Return of Menses After Discontinuation | Month 5 | 2 Participants |
| Mirena | Return of Menses After Discontinuation | Month 5 | 0 Participants |
| Mirena | Return of Menses After Discontinuation | Number (%) of Subjects With Onset of Menses Post-IUS Removal | 46 Participants |
| Mirena | Return of Menses After Discontinuation | Month 3 | 1 Participants |
| Mirena | Return of Menses After Discontinuation | Month 4 | 0 Participants |
| Mirena | Return of Menses After Discontinuation | Month 1 | 37 Participants |
| Mirena | Return of Menses After Discontinuation | Month 2 | 8 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Month 1 | 22 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Month 2 | 15 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Month 5 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Month 3 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Number (%) of Subjects With Onset of Menses Post-IUS Removal | 38 Participants |
| LNG20 (36-45 Yr Olds) | Return of Menses After Discontinuation | Month 4 | 1 Participants |
Secondary
Return to Fertility After Discontinuation
Subjects who discontinued from the trial and desired pregnancy were followed for up to 12 months to assess fertility after IUS removal.
Time frame: 12 months
Population: Distribution of Pregnancies (Months Post-IUS Removal) \[N(%)\]
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 11 | 5 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 8 | 16 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 5 | 20 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 2 | 36 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 7 | 15 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 6 | 18 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Total Number of Participants Pregnant | 201 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 1 | 17 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 10 | 5 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 3 | 34 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 12 | 1 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 9 | 6 Participants |
| LNG20 (16-35 Yr Olds) | Return to Fertility After Discontinuation | Month 4 | 28 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 6 | 1 Participants |
| Mirena | Return to Fertility After Discontinuation | Total Number of Participants Pregnant | 15 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 1 | 3 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 2 | 5 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 3 | 2 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 4 | 0 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 5 | 2 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 7 | 0 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 8 | 1 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 9 | 0 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 10 | 1 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 11 | 0 Participants |
| Mirena | Return to Fertility After Discontinuation | Month 12 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 8 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 3 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 11 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 9 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 2 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Total Number of Participants Pregnant | 2 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 10 | 1 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 6 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 5 | 1 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 1 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 7 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 4 | 0 Participants |
| LNG20 (36-45 Yr Olds) | Return to Fertility After Discontinuation | Month 12 | 0 Participants |
Secondary
Safety and Tolerability
The safety and tolerability based on the report of adverse events and serious adverse events
Time frame: 10 Years
Population: All Mirena participants were discontinued by end of Year 5.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LNG20 (16-35 Yr Olds) | Safety and Tolerability | Subjects Reporting at Least One SAE | 79 Participants |
| LNG20 (16-35 Yr Olds) | Safety and Tolerability | Subjects Reporting at Least One AE | 1441 Participants |
| LNG20 (16-35 Yr Olds) | Safety and Tolerability | Subjects Reporting No AE or SAE | 80 Participants |
| Mirena | Safety and Tolerability | Subjects Reporting at Least One SAE | 6 Participants |
| Mirena | Safety and Tolerability | Subjects Reporting at Least One AE | 138 Participants |
| Mirena | Safety and Tolerability | Subjects Reporting No AE or SAE | 15 Participants |
| LNG20 (36-45 Yr Olds) | Safety and Tolerability | Subjects Reporting at Least One AE | 137 Participants |
| LNG20 (36-45 Yr Olds) | Safety and Tolerability | Subjects Reporting No AE or SAE | 6 Participants |
| LNG20 (36-45 Yr Olds) | Safety and Tolerability | Subjects Reporting at Least One SAE | 8 Participants |