Clinical trial NCT03642210: Study of a Levonorgestrel 52 mg Intrauterine System for the Treatment of Heavy Menstrual Bleeding
Official title: A Phase 3, Multicenter, Open-Label Study of a Levonorgestrel 52 mg Intrauterine System for the Treatment of Heavy Menstrual Bleeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Menorrhagia
Lead sponsor: Medicines360
Sponsor class: OTHER
First posted: 2018-08-22
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Successful Treatment of Heavy Menstrual Bleeding
timeFrame: 6 months
Secondary outcomes:
measure: Menstrual Blood Loss - Percent Change From Baseline to Cycle 3 (28 Days Per Cycle; Approximately 3 Months)
timeFrame: 3 months
measure: Menstrual Blood Loss - Absolute Change in Baseline to Cycle 3 (28 Days Per Cycle; Approximately 3 Months)
timeFrame: 3 months
measure: Menstrual Blood Loss - Absolute Change From Baseline to Cycle 6 (28 Days Per Cycle; Approximately 6 Months)
timeFrame: 6 months
measure: Menstrual Blood Loss - Percent Change From Baseline to Cycle 6 (28 Days Per Cycle; Approximately 6 Months)
timeFrame: 6 months
measure: Change in Bleeding/Spotting Days From Baseline, Cycle 3, and Cycle 6.
timeFrame: 6 months
measure: Blood Changes - Hemoglobin
timeFrame: 6 months
measure: Blood Changes - Hematocrit
timeFrame: 6 months
measure: Blood Changes - Ferritin
timeFrame: 6 months
measure: Number of Participants That Discontinued vs Completed Full Treatment Duration
timeFrame: 6 months
measure: Participant Subjective Assessments
timeFrame: 6 months
measure: Changes in Number of Bleeding Episodes
timeFrame: 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: MomDoc Women's Health Research
state: Arizona
city: Sacramento
country: United States
facility: OB/GYN Research, University of California, Davis Health
state: California
city: San Diego
country: United States
facility: Wr-McCr, Llc
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center, OB-GYN Clinic
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Jacksonville
country: United States
facility: UF Health Women's Specialists
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Sandy Springs
country: United States
facility: WR-Mount Vernon Clinical Research, LLC
state: Georgia
city: Idaho Falls
country: United States
facility: CR Prime
state: Idaho
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Women's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Rex Garn Mabey
state: Nevada
city: Lawrenceville
country: United States
facility: Women's Health Research Center
state: New Jersey
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Company
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital, Center for Family Planning
state: Pennsylvania
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: WR-Medical Research Center of Memphis
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical-Conrad Clinical Research Center
state: Virginia
Study officials:
affiliation: COO
name: Andrea Olariu, MD, PhD
role: STUDY_DIRECTOR
References: