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
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
To compare the pharmacodynamic effects of 2 continuous dose regimens of ulipristal acetate
 5.0 and 10.0 mg-only oral contraception, versus a 24/4 day regimen of UPA 5.0 mg.
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.

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