Clinical trial: Efficacy Study of Two Continuous Regimens of Oral Daily 5 mg or 10 mg of Ulipristal Acetate (UPA), Versus a Dose of 5.0mg UPA for 24/4 Days (NCT01953679)

Eligibility criteria:
Inclusion Criteria:

          1. Women between 18 and 35 years old.

          2. In good health, with regular menstrual cycles that occur every 21-35 days.

               1. If subject is postpartum or post-abortal (with abortion in second trimester), she
                  will be required to have two normal menstrual cycles (3 menses) prior to
                  screening.

               2. If subject had an abortion in the first trimester, she will be required to have
                  at least one menstrual cycle (two menses) prior to screening.

          3. No current use of hormonal contraception or an intrauterine device and having had at
             least one complete menstrual cycle since having stopped hormonal contraception before
             starting the treatment.

             a. No use of injectable contraceptives (e.g. cyclofem or depo-medroxyprogesterone
             acetate) during the 6 months prior to screening unless the subject has returned to
             normal menses since last injection.

          4. Have a negative urine pregnancy test at the admission visit.

          5. Will not be at risk for pregnancy. They will be consistently using a non-hormonal
             method, barrier method with every act of intercourse until the time of study exit OR
             have a surgically sterile male partner with a vasectomy, must have undergone previous
             tubal ligation, be abstinent, or be in a same-sex relationship from the control period
             through study exit (including recovery period).

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

          7. Understand and sign an IRB approved inform consent form prior to screening activities
             (including fasting blood draws).

          8. Will have diastolic blood pressure (BP) ≤95 mm Hg and systolic BP ≤145 mm Hg after 5
             minutes in sitting position.

          9. BMI < 40 kg/m2 and not having previously undergone bariatric surgery.

         10. Agree not to participate in any other clinical trials during the course of this study.

        Exclusion Criteria:

          1. Women less than 18 and older than 35 years old.

          2. Women with menstrual cycle length of less than 21 or more than 35 days; or with
             spontaneous irregular menstrual cycle length with intra-individual variations of more
             than 5 days.

             a. If subject is postpartum or post-abortal (with abortion in second trimester) and
             not had two normal menstrual cycles (3 menses) prior to screening.

             b. If subject had an abortion in the first trimester and not had at least one
             menstrual cycle (two menses) prior to screening.

          3. Currently pregnant as confirmed by positive high-sensitivity urine pregnancy test.

          4. Unwilling to use a barrier method with every act of intercourse until study exit OR
             not have a surgically sterile male partner with a vasectomy, not have undergone
             previous tubal ligation, not abstinent, or not in a same-sex relationship from the
             control period through study exit (including recovery period).

          5. Women planning pregnancy within their months of study participation.

          6. Currently breast-feeding or within 30 days of discontinuing breast feeding, unless the
             woman has already had a menses following discontinuation of breast feeding.

          7. Current use of an IUD, or other hormonal contraception within last complete menstrual
             cycle prior to screening.

             a. Use of injectable contraceptives (e.g. cyclofem or depo-medroxyprogesterone
             acetate) during the 6 months prior to screening without the subject returning to
             normal menses since last injection.

          8. Undiagnosed abnormal genital bleeding.

          9. Known hypersensitivity to the active substance UPA or any of the excipients of the
             study treatment.

         10. Anomalies in endometrial appearance, TVUS or safety labs done at screening visit
             recognized as clinically significant by the investigator.

         11. Subject with a previous history of endometrial ablation.

         12. A clinically significant Pap test abnormality, as managed by current local or national
             guidelines. Women with a current abnormal Pap (within the last eighteen months):

               1. In accordance with the Bethesda system of classification: smear suggestive of
                  high-grade pre-cancerous lesion(s), including high grade squamous intraepithelial
                  lesions (HGSILs), are excluded; • Women with low grade squamous intraepithelial
                  lesion (LGSIL) or atypical squamous cells of undetermined significance
                  (ASCUS)/high-risk human papillomavirus (HPV) positive, or Atypical squamous
                  cells, cannot rule out a high grade lesion (ASC-H) may participate if further
                  evaluated with colposcopy and biopsy determines no evidence of a lesion with a
                  severity greater than cervical intraepithelial neoplasia (CIN) I. • Women with a
                  biopsy finding of CIN I should have follow-up for this finding per standard of
                  care; women are excluded if treatment is indicated.

               2. In accordance with other Pap class systems:

                  • Women with high grade dysplasia are excluded.

                  • Women with atypical glandular cells of undetermined significance (AGUS) are
                  excluded.

                  • Women with low grade dysplasia or CIN I interpretation on Pap test may
                  participate following exclusion of a high grade lesion by colposcopic evaluation
                  based on Investigator discretion and provided there is appropriate follow up in
                  accordance with local standards.

         13. Has 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 and history of ischemic heart disease or stroke while pregnant or taking
                  birth control pills;

               3. Acute deep venous thrombosis or pulmonary embolism;

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

               5. Benign and malignant liver tumors;

               6. Severe (decompensated) cirrhosis.

         14. Hereditary galactose intolerance, Lapp lactase deficiency , or glucose-galactose
             malabsorption.

         15. Known or suspected alcoholism or drug abuse.

         16. Known HIV infection.

         17. Smoking 15 cigarettes or more per day must be evaluated by the investigator or
             medically qualified designee for inclusion based on risk factors that would increase
             their risk for cardiovascular disease (CVD) and thromboembolism.

         18. Current or past deep vein thrombophlebitis or thromboembolic disorders.

         19. 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.

         20. Concomitant use of medication thought to interact with UPA (per SPCs):

               1. CYP3A4 inducers (rifampin, barbiturates, carbamazepine, bosentan, felbamate,
                  griseofulvin, oxcarbazepine, phenytoin, St John's Wort, topiramate),

               2. Other hormonal contraceptives including emergency contraception.

         21. Use of any medications that can interfere with the metabolism of hormone
             contraceptives, antibiotics that can interfere with metabolism of hormone
             contraceptives, and any drugs designated by the FDA as Pregnancy Category D or X.

         22. Current participation in any other trial of an investigational medicine or device or
             participation in the past three months before start of first treatment phase.

         23. Headaches with focal neurological symptoms only.

         24. Have diastolic blood pressure (BP) >95 mm Hg and systolic BP >145 mm Hg after 5
             minutes in sitting position.

               1. Hypertensive subjects who are treatment controlled and in the judgment of the
                  investigator are a good candidate require a waiver for participation.

         25. BMI ≥40 kg/m² or having previously undergone bariatric surgery.

         26. Have issues or concerns (in the judgment of the investigator) that may compromise the
             safety of the subject or confound the reliability of compliance and information
             acquired in this study.

             -
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 35 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