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


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Trial ID: NCT03642210


To assess the efficacy of a levonorgestrel 52 mg intrauterine system as a treatment for 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


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

      - 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

      - 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

      - 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

      - 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

   - 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


combination product: Levonorgestrel 52 mg intrauterine system


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kathryn Batham