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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,910
Unnamed facility
Phoenix, Arizona, United States
Unnamed facility
Palo Alto, California, United States
Number of Pregnancies Per Year
Number of pregnancies per year in each treatment arm.
Time frame: 10 years
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
Safety and Tolerability
The safety and tolerability based on the report of adverse events and serious adverse events
Time frame: 10 Years
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
Continuation Rates
The rate of continuation of usage over time.
Time frame: 10 Years
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Unnamed facility
San Francisco, California, United States
Unnamed facility
Vista, California, United States
Unnamed facility
Denver, Colorado, United States
Unnamed facility
Atlanta, Georgia, United States
Unnamed facility
Idaho Falls, Idaho, United States
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Des Moines, Iowa, United States
Unnamed facility
Ann Arbor, Michigan, United States
...and 15 more locations
Time frame: 5 months
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
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
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
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
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
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
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
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
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
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