Study of a Levonorgestrel 52 mg Intrauterine System for the Treatment of Heavy Menstrual Bleeding

A Phase 3, Multicenter, Open-Label Study of a Levonorgestrel 52 mg Intrauterine System for the Treatment of Heavy Menstrual Bleeding

To assess the efficacy of a levonorgestrel 52 mg intrauterine system as a treatment for heavy menstrual bleeding.

Study Overview

• Status: Completed
• Conditions: Menorrhagia
• Intervention / Treatment: Combination product: Levonorgestrel 52 mg intrauterine system

Detailed Description

This study is a multicenter, open-label, evaluation of the efficacy and safety of LNG20 IUS for treatment of heavy menstrual bleeding.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • MomDoc Women's Health Research
  • California
    • Sacramento, California, United States, 95817
      • OB/GYN Research, University of California, Davis Health
    • San Diego, California, United States, 92108
      • Wr-McCr, Llc
    • Stanford, California, United States, 94403
      • Stanford University Medical Center, OB-GYN Clinic
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Jacksonville, Florida, United States, 32207
      • UF Health Women's Specialists
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials, Llc
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Sandy Springs, Georgia, United States, 30328
      • WR-Mount Vernon Clinical Research, LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • CR Prime
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Women's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University in St. Louis School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Rex Garn Mabey
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Women's Health Research Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Physicians Company
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital, Center for Family Planning
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Memphis, Tennessee, United States, 30328
      • WR-Medical Research Center of Memphis
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical-Conrad Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent
• Reports subjectively heavy menses for most menses when not using hormonal contraception or a copper IUD
• Healthy females 18-50 years old, inclusive, at the time of enrollment
• Able to read and write, as determined by study personnel
• FSH value ≤30 mIU/mL at screening
• Typical menstrual cycle length of 21-35 days with variation from cycle to cycle of typically 5 days or less
• Has menstrual blood loss in 2 of the 3 cycles during the Screening Phase with ≥ 80 mL per cycle as measured by the AH method
• Uterine sound depth of ≥5.5 cm
• Willing to comply with study visit schedule and assessments, including sanitary product collection and diary completion requirements
• Documented (i.e., printed report) Pap testing, regardless of subject's age, and any indicated evaluation/treatment that demonstrates no need for further evaluation during the course of study participation (i.e., within 10 months after consent)
• Planning to reside within a reasonable driving distance of a research site (approximately 150 miles) for duration of study participation
• Willing to use a medication other than a NSAID as first-line treatment for any pain condition during the duration of study participation
• Willing to abstain from heterosexual intercourse or use acceptable contraception during the screening phase; acceptable contraception includes male or female permanent contraception, withdrawal (if has been using as current method prior to screening) or a barrier method
• If previously pregnant, at least one subjectively heavy menses prior to screening

Exclusion Criteria:

• Currently pregnant
• Planning to attempt to become pregnant during the screening and treatment phases of study participation (i.e., up to approximately 11 months after consent)
• Currently lactating or not having a subjectively heavy menses since discontinuation of lactation prior to screening
• Clinical diagnosis of perimenopause (in the opinion of the investigator) based on one or more of the following: changes in menstrual regularity (e.g., shorter, longer, absent, irregular), hot flashes, sleeping disorder, or changes in mood (e.g., depression, nervous tension, and irritability) within 3 months prior to or during the screening period
• Screening blood laboratory value outside of the normal range that, in the opinion of the investigator, requires treatment or further work-up (i.e., are considered clinically significant)
• Has poor venous access or significant history of inability to have blood samples drawn
• Body habitus or history of lower genital tract abnormalities or prior surgeries which may prohibit proper visualization of the cervix or not allow the uterus to be appropriately instrumented
• History of bicornuate uterus or any other abnormality of the uterus resulting in distortion of the uterine cavity or cervical canal incompatible with insertion

• Prior (documented within 6 months) or baseline study ultrasound examination demonstrating:

  • A congenital or acquired uterine anomaly that distorts the uterine cavity or cervical canal incompatible with insertion;
  • Endometrial polyps (unless previously removed),
  • Fibroids meeting any of the following criteria: Distort the uterine cavity or cervical canal incompatible with insertion; Submucosal location; Exceeding 2 cm in the greatest dimension for any individual fibroid; More than three fibroids of at least 1.5 cm in greatest diameter
  • Clear evidence of adenomyosis consisting of any of the following: Subendometrial cysts; Diffuse adenomyosis based on a heterogeneous myometrial echotexture consisting of Hyperechoic findings (islands of endometrial glands), hypoechoic findings (associated muscle hypertrophy), or "Venetian blind" appearance due to subendometrial echogenic linear striations and acoustic shadowing where endometrial tissues cause a hyperplastic reaction.
• Recently diagnosed or clinically evident cervicitis or upper genital tract infection at the time of IUS insertion (unless successfully treated and considered clinically cured for at least 7 days prior to enrollment)
• History of pelvic actinomycosis infection (i.e., received antibiotic treatment; criterion does not include solely a history of Pap test with actinomyces)
• Postpartum or post-abortion endometritis unless symptoms resolved at least 4 weeks prior to screening
• Chronic endometritis on endometrial biopsy at screening (an endometrial biopsy performed within 6 months of Visit 1 could be used if a report is available with a tissue diagnosis)

• Has any of the following premalignant or malignant diseases:

  • Malignant melanoma
  • Acute malignancies affecting blood or leukemias
  • Gestational trophoblastic disease (unless at least one year with undetectable beta-hCG)
  • Known or suspected cervical, ovarian, vaginal or vulvar cancer
  • Uterine cancer or evidence of uterine malignancy, endometrial intraepithelial neoplasia (EIN) or hyperplasia on an endometrial biopsy at screening (an endometrial biopsy performed within 6 months of Visit 1 could be used if a report is available with a tissue diagnosis)
  • History of breast cancer, or suspicion of breast cancer until proven otherwise

• Has any of the following medical conditions:

  • Bleeding diathesis (inherited or acquired)
  • History of von Willebrand's disease or other known coagulopathy
  • Uncontrolled significant hypertension defined as a sitting systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 95 mm Hg at any screening or enrollment visit unless treated and controlled within two weeks of discovery
  • Presence or history of venous thromboembolic diseases (deep vein thrombosis, pulmonary embolism), presence or history of arterial thromboembolic diseases (e.g., myocardial infarction, stroke)
  • Uncontrolled thyroid disorder
  • Sickle cell anemia
  • Diabetes mellitus that is poorly controlled or with end-organ/vascular complications
  • Hyperprolactinemia at screening
  • Acute or severe liver disease or liver tumor
  • Poorly controlled bipolar disorder, schizophrenia, psychosis, major depressive disorder or other major psychiatric disorder according the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-5)
  • History of a positive HIV test or having a partner who is known to be HIV positive
  • Current or history of alcohol, illicit drug or prescription drug abuse within 12 months prior to screening
• Use of antifibrinolytics, platelet aggregation inhibitors, anticoagulants or other similar medications that can increase or decrease bleeding within 30 days prior to and during the screening (EXCEPTION: NSAIDs can be used as second-line treatment for pain management)
• Use of intrauterine or implantable contraception, progestin-only pills, combined hormonal contraceptives or oral progestin therapy within 30 days before screening
• Depomedroxyprogesterone acetate (DMPA) injection within the past 9 months prior to screening (this exclusionary time period can be shortened to 6 months if the subject has also had two spontaneous menstrual cycles [requires minimum of 3 heavy menses] that meet criteria for normal menstrual cycle pattern)
• Use of non-contraceptive estrogen, progesterone, progestin, testosterone, androgen or other gonadotropins (e.g. hCG) within 30 days before screening
• Prior total or partial endometrial ablation or resection
• History of a uterine aspiration or curettage procedure for any indication (other than an office biopsy) within 4 weeks of screening
• Known or suspected allergy to levonorgestrel or hypersensitivity to any component of the product
• Use of an experimental medication or receipt of an experimental treatment for any condition within 30 days of screening
• Study staff or a member of the immediate family of a study staff
• Any condition or circumstance that, in the opinion of the Investigator, would constitute contraindications to participation in the study or would compromise ability to comply with the study protocol, such as any concurrent medical condition that is not stable and well-controlled, that is likely to worsen, or that may require recurrent hospitalizations during study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levonorgestrel 52 mg intrauterine system; Levonorgestrel 52 mg intrauterine system, inserted for use up to 6 months	Combination product: Levonorgestrel 52 mg intrauterine system; Levonorgestrel 52 mg intrauterine system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Successful Treatment of Heavy Menstrual Bleeding	Number of participants who completed treatment with an End-of-Treatment menstrual blood loss of <80 ml or ≤50% of baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual Blood Loss - Percent Change From Baseline to Cycle 3 (28 Days Per Cycle; Approximately 3 Months)	• Percent change from Baseline MBL to mid-treatment MBL Cycle 3 (28 days per cycle; approximately 3 months)	3 months
Menstrual Blood Loss - Absolute Change in Baseline to Cycle 3 (28 Days Per Cycle; Approximately 3 Months)	• Absolute change in Baseline MBL to mid-treatment MBL Cycle 3 (28 Days Per Cycle; Approximately 3 Months)	3 months
Menstrual Blood Loss - Absolute Change From Baseline to Cycle 6 (28 Days Per Cycle; Approximately 6 Months)	• Absolute change from Baseline to end-of-treatment MBL Cycle 6 (28 Days Per Cycle; Approximately 6 Months)	6 months
Menstrual Blood Loss - Percent Change From Baseline to Cycle 6 (28 Days Per Cycle; Approximately 6 Months)	• Percent change from Baseline MBL to end-of-treatment MBL Cycle 6 (28 Days Per Cycle; Approximately 6 Months)	6 months
Change in Bleeding/Spotting Days From Baseline, Cycle 3, and Cycle 6.	Number of days bleeding, spotting, and bleeding and/or spotting at Baseline, Cycle 3 (approximately 3 months), and Cycle 6 (approximately 6 months).	6 months
Blood Changes - Hemoglobin	• Percent change in hemoglobin from Baseline to mid-treatment (approximately 3 months), from Baseline to end-of-treatment (approximately 6 months), and from mid-treatment to end-of-treatment (approximately 3 months).	6 months
Blood Changes - Hematocrit	• Percent change in hematocrit from Baseline to mid-treatment (approximately 3 months), from Baseline to end-of-treatment (approximately 6 months), and from mid-treatment to end-of-treatment (approximately 3 months).	6 months
Blood Changes - Ferritin	Change in serum ferritin from Baseline to mid-treatment (approximately 3 months) and to end-of-treatment (approximately 6 months).	6 months
Number of Participants That Discontinued vs Completed Full Treatment Duration	Number of Participants that Discontinued vs Completed Full Treatment Duration.	6 months
Participant Subjective Assessments	• Subjective assessment of menstrual bleeding changes based on VAS questionnaires of Safety and Continuation Rates from Baseline to Treatment Cycle 3 (approximately 3 months) to Cycle 6 (approximately 6 months). Participants responded to various questions regarding their menstrual bleeding on Visual Analog Scales (VAS), with "Not Acceptable" at 0 cm and "Completely Acceptable" at 10 cm.	6 months
Changes in Number of Bleeding Episodes	• Changes from Baseline to mid-treatment Cycle 3 (approximately 3 months), from Baseline to end of treatment Cycle 6 (approximately 6 months), and from mid-treatment Cycle 3 to end of treatment Cycle 6 in the number of bleeding episodes. Bleeding episodes are defined as all bleeding days separated by no more than one bleeding-free day.	6 months

Collaborators and Investigators

• Sponsor: Medicines360
• Investigators: Study Director: Andrea Olariu, MD, PhD, COO

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): October 12, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Menstruation Disturbances; Uterine Hemorrhage; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Menorrhagia; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: M360-L105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No