A Study of a Levonorgestrel-Releasing Intrauterine System for Long-Term, Reversible Contraception

Phase 3

Terminated

Conditions: Contraception

Interventions: Drug: Mirena
Drug: LNG20

Registration Number: NCT00995150

Lead Sponsor: Medicines360

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

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 1910

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mirena	Mirena	Levonorgestrel-releasing intrauterine system for contraception
LNG20 (36-45 Year Olds)	LNG20	LNG20 levonorgestrel-releasing intrauterine system in subjects 36-45 years of age
LNG20 (16-35 Year Olds)	LNG20	LNG20 levonorgestrel-releasing intrauterine system in subjects 16-35 years of age

Primary Outcome Measures

Name	Time	Method
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.
Number of Pregnancies Per Year	10 years	Number of pregnancies per year in each treatment arm.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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
Expulsion Rate	10 years	The expulsion rate includes the number of subjects with reported expulsions or removal of the IUS, regardless of reason.
Continuation Rates	10 Years	The rate of continuation of usage over time.
Safety and Tolerability	10 Years	The safety and tolerability based on the report of adverse events and serious adverse events
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.
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.
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.
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.
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.