Clinical trial: Study of a Levonorgestrel 52 mg Intrauterine System for the Treatment of Heavy Menstrual Bleeding (NCT03642210)

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
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 50 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? 0