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ContraceptionPhase 3NCT00995150

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

A Phase 3 study testing LNG20 and Mirena in people with Contraception, run by Medicines360 at 25 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Contraception
What is being tested?
LNG20 and Mirena
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,910 participants
Where
25 sitesUnited States
Study dates
Nov 2009to 12 Oct 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • Healthy women requesting contraception
  • 16-35 years old
  • Cohort 36-45 years old
  • Sexually active

Who cannot join

  • 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

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • Study site

    Ann Arbor, Michigan

  • Study site

    Atlanta, Georgia

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Denver, Colorado

  • Study site

    Des Moines, Iowa

  • Study site

    Houston, Texas

  • Study site

    Idaho Falls, Idaho

  • Study site

    New York, New York

  • Study site

    Norfolk, Virginia

  • Study site

    Palo Alto, California

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Magee Women's Hospital, University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Study site

    Portland, Oregon

  • Study site

    Salt Lake City, Utah

  • Study site

    San Francisco, California

  • Study site

    Seattle, Washington

  • Study site

    St Louis, Missouri

  • Study site

    Tulsa, Oklahoma

  • Study site

    Vista, California

Other trials in United States

About this study

Official title: A Phase 3, Multi-Center, Open-Label Study of a Levonorgestrel-Releasing Intrauterine System for Long-Term, Reversible Contraception

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.

Read the 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

Conditions
Contraception
Being tested
LNG20, Mirena
Keywords
contraception, intrauterine, long-term, reversible

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LNG20Drug

    Also called Liletta

    levonorgestrel-releasing intrauterine system for contraception

  • MirenaDrug

    Mirena intrauterine system

Study groups in NCT00995150
Study groupRoleWhat they receive
LNG20 (16-35 Year Olds)ExperimentalLNG20 levonorgestrel-releasing intrauterine system in subjects 16-35 years of age
Receives: Drug: LNG20
MirenaActive comparatorLevonorgestrel-releasing intrauterine system for contraception
Receives: Drug: Mirena
LNG20 (36-45 Year Olds)ExperimentalLNG20 levonorgestrel-releasing intrauterine system in subjects 36-45 years of age
Receives: Drug: LNG20

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Pregnancies Per Year

    Number of pregnancies per year in each treatment arm.

    Measured: 10 years

  2. 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.

    Measured: 8 years

Secondary outcomes (14)

  1. Safety and Tolerability

    The safety and tolerability based on the report of adverse events and serious adverse events

    Measured: 10 Years

  2. 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.

    Measured: 8 Years

  3. Continuation Rates

    The rate of continuation of usage over time.

    Measured: 10 Years

  4. 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.

    Measured: 5 months

  5. 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.

    Measured: 12 months

  6. 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.

    Measured: 5 Years

  7. 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.

    Measured: month 36 through 120

  8. 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.

    Measured: 10 Years

  9. 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

    Measured: 8 Years

  10. Incidence of Bleeding and/or Spotting

    From data based on the daily diary log, number of IUS subjects experiencing some bleeding and/or spotting.

    Measured: 8 Years

  11. 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.

    Measured: 8 years

  12. Expulsion Rate

    The expulsion rate includes the number of subjects with reported expulsions or removal of the IUS, regardless of reason.

    Measured: 10 years

  13. 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.

    Measured: 10 years

  14. 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.

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2009 (estimated)
  2. Study startNov 2009
  3. Primary completion12 Oct 2021
  4. Study completion12 Oct 2021

Why it stopped: The data cutoff date of 05 April 2021 was chosen as it coincides with all subjects completing through Year 8 of use (intended duration of use for the product).

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,910 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00995150
Sponsor's protocol ID
M360-L102
Status last verified
Jul 2024
First submitted
13 Oct 2009
Last updated
14 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kerns JL, Keder LM, Cwiak CA, Westhoff CL, Creinin MD. Hormone-related side effects in new users of a levonorgestrel 52-mg intrauterine device. Am J Obstet Gynecol. 2024 Dec;231(6):628.e1-628.e10. doi: 10.1016/j.ajog.2024.06.049. Epub 2024 Jul 3.

    PubMed 38969201

  • Chen BA, Kimble T, Harris LH, Kerns JL, Olariu AI, Creinin MD. Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use. Obstet Gynecol. 2023 May 1;141(5):1004-1006. doi: 10.1097/AOG.0000000000005147. Epub 2023 Apr 5.

    PubMed 37023451

  • Chen BA, Eisenberg DL, Schreiber CA, Turok DK, Olariu AI, Creinin MD. Bleeding changes after levonorgestrel 52-mg intrauterine system insertion for contraception in women with self-reported heavy menstrual bleeding. Am J Obstet Gynecol. 2020 Apr;222(4S):S888.e1-S888.e6. doi: 10.1016/j.ajog.2019.11.1288. Epub 2019 Dec 19.

    PubMed 31866516

  • Teal SB, Turok DK, Chen BA, Kimble T, Olariu AI, Creinin MD. Five-Year Contraceptive Efficacy and Safety of a Levonorgestrel 52-mg Intrauterine System. Obstet Gynecol. 2019 Jan;133(1):63-70. doi: 10.1097/AOG.0000000000003034.

    PubMed 30531565

  • Schreiber CA, Teal SB, Blumenthal PD, Keder LM, Olariu AI, Creinin MD. Bleeding patterns for the Liletta(R) levonorgestrel 52 mg intrauterine system. Eur J Contracept Reprod Health Care. 2018 Apr;23(2):116-120. doi: 10.1080/13625187.2018.1449825. Epub 2018 Mar 21.

    PubMed 29560743

  • Darney PD, Stuart GS, Thomas MA, Cwiak C, Olariu A, Creinin MD. Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg intrauterine system use. Contraception. 2018 Mar;97(3):210-214. doi: 10.1016/j.contraception.2017.10.005. Epub 2017 Oct 13.

    PubMed 29038072

  • Creinin MD, Jansen R, Starr RM, Gobburu J, Gopalakrishnan M, Olariu A. Levonorgestrel release rates over 5 years with the Liletta(R) 52-mg intrauterine system. Contraception. 2016 Oct;94(4):353-6. doi: 10.1016/j.contraception.2016.04.010. Epub 2016 Apr 25.

    PubMed 27125892

  • Eisenberg DL, Schreiber CA, Turok DK, Teal SB, Westhoff CL, Creinin MD; ACCESS IUS Investigators. Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system. Contraception. 2015 Jul;92(1):10-6. doi: 10.1016/j.contraception.2015.04.006. Epub 2015 Apr 28.

    PubMed 25934164

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LNG20 and Mirena in people with Contraception, run by Medicines360 at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Pregnancies Per Year (time frame: 10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00995150, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024.

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