Study Comparing Emergency Contraception Effectiveness in Women Who Weight ≥ 80 kg
Study Comparing Emergency Contraception Effectiveness in Women Who Weight ≥ 80 kg
The proposed research study is a Phase IIb, multi-center, single-blind, randomized study of
 UPA 30 mg, LNG 1.5 mg and LNG 3.0 mg to evaluate EC effectiveness in women with weight ≥ 80
 kg who present within 72 hours of unprotected intercourse.
Orally-dosed emergency contraception (EC) is highly effective when used properly. EC is up to
 90% effective at preventing pregnancy following unprotected intercourse. Both ulipristal
 acetate (UPA) and levonorgestrel (LNG) delay or inhibit ovulation when used for EC. For
 individual women, use of EC provides a critical backup to prevent unintended pregnancy.

 However, obesity may severely impair EC effectiveness. Data from two large randomized control
 trials to identify risk factors for EC failure. A woman of obese body mass index (BMI)
 (≥30mg/kg2) using LNG-based EC had more than a 4 times greater risk of pregnancy compared to
 her normal BMI counterpart and a woman of overweight BMI (25-29.9) was at twice the risk of
 pregnancy. Failure was also associated with a high body weight. LNG-based EC appears to have
 a ceiling of efficacy at 70 kg and no efficacy for women 80 kg and above. It is believed that
 by doubling the dose to LNG 3.0 mg, serum levels of LNG are corrected to a therapeutic range.
Inclusion Criteria:

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

 2. Between 18 and 40 years inclusive at the enrollment visit.

 3. Weight ≥ 80 kg.

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

 5. If subject is postpartum or post-abortal, she must have experienced a menstrual bleed
 since the pregnancy ended

 6. If a subject recently used non-injectable hormonal contraception, one bleeding episode
 consistent with menses must have occurred since last use;

 7. Willing to avoid use of any hormonal or intrauterine contraception until the end of
 the study;

 8. For women with a recent history of Depo Provera use, the most recent injection must
 have been at least 6 months before study entry, and the subject must have had at least
 one normal menstrual cycle (2 consecutive menses);

 9. Request emergency contraception within 72 hours (3 days) after unprotected coitus, as
 defined by lack of contraceptive use, condom breakage (including condoms lubricated
 with spermicide), or other barrier contraceptive method failure;

 10. Have a negative urine pregnancy test at time of screening

 11. Reports all acts of unprotected coitus since her prior menses are within 72 hours
 prior to enrollment;

 12. Willing to abstain from further acts of unprotected intercourse until the end of the
 study;

 13. Give voluntary, written informed consent, and agree to observe all study requirements
 including being available for follow up for at least the next 4 weeks;

 14. Accepts that the risk of pregnancy with oral EC is greater than that following
 placement of a copper IUD for EC.

 Exclusion Criteria:

 1. Be currently pregnant (positive high-sensitivity urine pregnancy test);

 2. Be currently breastfeeding or within 30 days of discontinuing breastfeeding, unless
 the subject has already had a menses following discontinuation of breastfeeding;

 3. Desire to use hormonal systemic contraception within 5 days of study drug use

 4. Have had a female sterilization procedure;

 5. Have a partner with a history of vasectomy;

 6. Current inability to tolerate oral medication;

 7. Have impaired hypothalamic-pituitary-adrenal reserve or oral glucocorticoid
 replacement therapy in the last year.

 8. Have known liver disease;

 9. Have known liver abnormalities with elevated enzymes at least twice the upper limit of
 normal requiring use of liver enzyme inducers.

 10. Have known hypersensitivity to the active substance UPA or LNG, or any of the
 excipients of the study treatment.

 11. Have a current need for exogenous hormones.

 12. Have concomitant use of strong CYP3A4 inhibitors (as identified by the FDA) or
 inducers at the time of or planned use within 3 days of dosing;

 13. Use any medications that can interfere with the metabolism of hormonal contraceptives;
 take antibiotics that can interfere with metabolism of hormonal contraceptives at the
 time of or planned use within 3 days of dosing of the study drug; or use any drugs
 designated by the FDA as falling in the Pregnancy and Lactation narrative subsections
 (formerly Category D or X medications).

 14. Current or recent (within one month) participation in any other trial of an
 investigational medicine or device or planning to participate in another clinical
 trial during this study.

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

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

 17. Have used UPA or LNG EC within 30 days prior to enrollment and not had a menses since
 using the drug.

 18. Be a site staff member with delegated study responsibilities or a family member of a
 site staff member with delegated study responsibilities. -