Clinical trial: Study of the Safety and Efficacy of Ulipristal Acetate (UPA) Used Daily as a Contraceptive (NCT03296098)

Eligibility criteria:
Inclusion Criteria:

        To enroll into the clinical trial, potential subjects must:

          1. Be in good general overall health with no chronic medical conditions that result in
             periodic exacerbations that require significant medical care.

          2. Be women between 18 and 35 years inclusive at the enrollment visit.

          3. Have regular menstrual cycles that occur every 21-35 days when not using hormonal
             contraception.

             a. If subject is postpartum or post-abortal, she must have one menstrual bleed prior
             to enrollment.

          4. Be seeking contraception, and willing to use the study drug as the only contraception
             method during their months of study participation.

          5. If using a ring, patch, pill, or implant prior to study treatment, the subject must
             discontinue the active hormone at least 4 days, and no more than 7 days, prior to
             study drug initiation. Note that for combined oral contraceptive users, placebo pills
             are not counted as active hormone.

          6. If using a hormonal intrauterine device (IUD) prior to study treatment, the IUD must
             be removed prior to study drug initiation; removal and study drug initiation can occur
             on the same day, but the subject must refrain from sexual intercourse for 7 days
             following IUD removal.

          7. If using a copper IUD prior to study treatment, the IUD must be removed prior to study
             drug initiation; removal and study drug initiation can occur on the same day. The IUD
             removal and study drug initiation must occur during the first 7 days of a spontaneous
             menses.

          8. If using a non-hormonal contraceptive method (e.g. condoms or withdrawal) prior to
             study treatment, drug initiation should occur within the first 7 days of a spontaneous
             menses.

          9. If the woman has received a long-acting injectable contraceptive (e.g.
             depomedroxyprogesterone acetate) during the 10 months prior to screening, she must
             have resumed cyclic spontaneous menses (two menstrual bleeds) since last injection.

         10. Have a negative urine pregnancy test at the enrollment visit.

         11. Have an intact uterus and both ovaries.

         12. In the opinion of the investigator, be willing and able to follow all study
             requirements, including use of the study product and be willing to record requested
             information on a daily diary.

         13. Understand and sign an (Institutional Review Board) IRB approved informed consent form
             prior to screening activities (including fasting blood draws).

         14. Have a diastolic blood pressure (BP) ≤95 mm Hg and systolic BP ≤145 mm Hg after 5
             minutes in a sitting position at the enrollment visit. Hypertensive subjects who are
             treatment controlled and, in the judgment of the investigator, are good candidates
             require a waiver for participation.

         15. Have a body mass index (BMI) < 40 kg/m2.

         16. Be planning to have at least one act of heterosexual vaginal intercourse each month
             during study participation.

         17. Be willing to accept an unknown risk of pregnancy during study participation.

        Exclusion Criteria:

        To enroll into the clinical trial, potential subjects must not:

          1. Be women with irregular menstrual cycles defined as a variation in cycle length of
             more than 5 days.

          2. Be planning pregnancy within their months of study participation.

          3. Be currently breast-feeding or within 30 days of discontinuing breast feeding, unless
             the subject has already had a menses following discontinuation of breast feeding.

          4. Have undiagnosed abnormal genital bleeding.

          5. Have known hypersensitivity to the active substance UPA or any of the excipients of
             the study treatment.

          6. Have a history of endometrial hyperplasia or malignancy.

          7. Have abnormal Transvaginal Ultrasound (TVUS) or safety labs done at the screening
             visit recognized as clinically significant by the investigator (or medically qualified
             designee).

          8. Have a previous history of endometrial ablation.

          9. Have a previous history of liver disease or screening liver enzyme results more than
             three times the upper limit of normal values.

         10. Have a known clinically significant Pap test abnormality, as managed by current local
             or national guidelines, that would require treatment during study participation.

         11. Have any of the following known contraindication to progestin-only oral contraceptive
             (OC):

               1. History or existing breast cancer, or other hormone sensitive neoplasia;

               2. Current or history of ischemic heart disease or stroke while pregnant or taking
                  birth control pills;

               3. Systemic Lupus Erythematosus with positive or unknown antiphospholipid
                  antibodies;

               4. Benign or malignant liver tumors;

               5. Severe (decompensated) cirrhosis.

         12. Have known or suspected alcoholism or drug abuse.

         13. Have known HIV infection.

         14. Have an anticipated need for regular condom use as defined as use of at least one
             condom per month after enrollment.

         15. Have previously participated in the study.

         16. Have a current need for exogenous hormones or therapeutic anticoagulants.

         17. Have a current or history of deep vein thromboembolic disorder or aortic
             thromboembolism, including stroke and myocardial infarction

         18. Have a current or past medically diagnosed severe depression, which, in the opinion of
             the investigator, could be exacerbated by use of a hormonal contraceptive, unless she
             is stable on antidepressant medication.

         19. Have concomitant use of medication thought to interact with UPA (per Summary of
             Product Characteristics (SPCs)) such as CYP3A4 inducers (rifampin, barbiturates,
             carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, phenytoin, St John's
             Wort, topiramate).

         20. Have concomitant use of moderate or strong CYP3A4 inhibitors as identified by the FDA.
             Subjects who begin use of a moderate CYP3A4 inhibitor after study enrollment require a
             waiver to continue in the study.

         21. Use any medications that can interfere with the metabolism of hormonal contraceptives,
             antibiotics that can interfere with metabolism of hormonal contraceptives, or any
             drugs designated by the FDA as falling in the Pregnancy and Lactation narrative
             subsections (formerly Category D or X medications).

         22. Currently participate in any other trial of an investigational medicine or device or
             have participated in the three months before start of treatment or be planning to
             participate in another clinical trial during this study.

         23. Have a history of a bariatric surgery procedure associated with malabsorption.

         24. Be planning to undergo major surgery during study participation.

         25. Live outside of the catchment area of the study site.

         26. Have used UPA, including Ella, within 30 days prior to enrollment and not had a menses
             since using UPA.

         27. Any site staff member with delegated study responsibilities or a family member of a
             site staff member with delegated study responsibilities.
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 35 Years

Patient description (medical language): A 23-year-old female has prolonged oral bleeding immediately after a tooth extraction.  Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration.  The patient has heavy menstrual cycles each month.  She has no other medical problems and takes no medications.  Her mother and grandmother have also had excessive bleeding during menstrual period.  Review of systems is positive for mild bruising on his legs. Laboratory findings reveal a normal platelet count and an abnormal ristocetin cofactor assay, as well as CB <= 0.30 IU/mL and FVIII:C <= 0.40 IU/mL.

Patient description (patient's own words): I'm a 23 woman and I went to the ER because of non-stop bleeding after my tooth extraction. I tried to make the bleeding stop but it just kept going for hours and it finally stopped when I took some medication called DDAVP. I usually have heavy periods, just like my mom and grandma had. I don't have any other medical condition and I don't take any other medication. The doctor noticed the bruises on my legs. I had to do some lab tests. I had a normal platelet count but an abnormal ristocetin cofactor assay. I had low CB and FVIII:C levels.

Does the patient match the trial criteria? 1