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 hormonalcontraception 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 oftypically 5 days or less

• Has menstrual blood loss in 2 of the 3 cycles during the Screening Phase with ≥ 80mL 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 sanitaryproduct collection and diary completion requirements

• Documented (i.e., printed report) Pap testing, regardless of subject's age, and anyindicated evaluation/treatment that demonstrates no need for further evaluationduring 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 paincondition during the duration of study participation

• Willing to abstain from heterosexual intercourse or use acceptable contraceptionduring the screening phase; acceptable contraception includes male or femalepermanent contraception, withdrawal (if has been using as current method prior toscreening) 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 ofstudy participation (i.e., up to approximately 11 months after consent)

• Currently lactating or not having a subjectively heavy menses since discontinuationof lactation prior to screening

• Clinical diagnosis of perimenopause (in the opinion of the investigator) based onone 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 orduring the screening period

• Screening blood laboratory value outside of the normal range that, in the opinion ofthe investigator, requires treatment or further work-up (i.e., are consideredclinically significant)

• Has poor venous access or significant history of inability to have blood samplesdrawn

• Body habitus or history of lower genital tract abnormalities or prior surgerieswhich may prohibit proper visualization of the cervix or not allow the uterus to beappropriately instrumented

• History of bicornuate uterus or any other abnormality of the uterus resulting indistortion of the uterine cavity or cervical canal incompatible with insertion

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

• A congenital or acquired uterine anomaly that distorts the uterine cavity orcervical canal incompatible with insertion;

• Endometrial polyps (unless previously removed),

• Fibroids meeting any of the following criteria: Distort the uterine cavity orcervical canal incompatible with insertion; Submucosal location; Exceeding 2 cmin the greatest dimension for any individual fibroid; More than three fibroidsof 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 myometrialechotexture consisting of Hyperechoic findings (islands of endometrial glands),hypoechoic findings (associated muscle hypertrophy), or "Venetian blind"appearance due to subendometrial echogenic linear striations and acousticshadowing where endometrial tissues cause a hyperplastic reaction.

• Recently diagnosed or clinically evident cervicitis or upper genital tract infectionat the time of IUS insertion (unless successfully treated and considered clinicallycured 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 weeksprior to screening

• Chronic endometritis on endometrial biopsy at screening (an endometrial biopsyperformed within 6 months of Visit 1 could be used if a report is available with atissue 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 undetectablebeta-hCG)

• Known or suspected cervical, ovarian, vaginal or vulvar cancer

• Uterine cancer or evidence of uterine malignancy, endometrial intraepithelialneoplasia (EIN) or hyperplasia on an endometrial biopsy at screening (anendometrial biopsy performed within 6 months of Visit 1 could be used if areport 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 bloodpressure ≥ 160 mm Hg or diastolic blood pressure ≥ 95 mm Hg at any screening orenrollment 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/vascularcomplications

• Hyperprolactinemia at screening

• Acute or severe liver disease or liver tumor

• Poorly controlled bipolar disorder, schizophrenia, psychosis, major depressivedisorder or other major psychiatric disorder according the criteria of theDiagnostic 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 HIVpositive

• 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 othersimilar medications that can increase or decrease bleeding within 30 days prior toand during the screening (EXCEPTION: NSAIDs can be used as second-line treatment forpain management)

• Use of intrauterine or implantable contraception, progestin-only pills, combinedhormonal contraceptives or oral progestin therapy within 30 days before screening

• Depomedroxyprogesterone acetate (DMPA) injection within the past 9 months prior toscreening (this exclusionary time period can be shortened to 6 months if the subjecthas 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, androgenor 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 (otherthan an office biopsy) within 4 weeks of screening

• Known or suspected allergy to levonorgestrel or hypersensitivity to any component ofthe product

• Use of an experimental medication or receipt of an experimental treatment for anycondition 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, wouldconstitute contraindications to participation in the study or would compromiseability to comply with the study protocol, such as any concurrent medical conditionthat is not stable and well-controlled, that is likely to worsen, or that mayrequire recurrent hospitalizations during study participation