Study Comparing Emergency Contraception Effectiveness in Women Who Weight ≥ 80 kg

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multi-center, Randomized Study of the Efficacy of Ulipristal Acetate (UPA) 30 mg, Levonorgestrel (LNG) 1.5 mg, and LNG 3.0 mg for Emergency Contraception (EC) in Women With Weight ≥ 80 kg

Conditions
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Contraception

Intervention / Treatment
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* Drug: Ulipristal Acetate
* Drug: Levonorgestrel
* Drug: Levonorgestrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be in good general overall health with no chronic medical conditions that result in periodic exacerbations that require significant medical care. Between 18 and 40 years inclusive at the enrollment visit. Weight ≥ 80 kg. Have regular menstrual cycles that typically occur every 21-35 days when not using hormonal contraception. If subject is postpartum or post-abortal, she must have experienced a menstrual bleed since the pregnancy ended If a subject recently used non-injectable hormonal contraception, one bleeding episode consistent with menses must have occurred since last use; Willing to avoid use of any hormonal or intrauterine contraception until the end of the study; 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); 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; Have a negative urine pregnancy test at time of screening Reports all acts of unprotected coitus since her prior menses are within 72 hours prior to enrollment; Willing to abstain from further acts of unprotected intercourse until the end of the study; 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; Accepts that the risk of pregnancy with oral EC is greater than that following placement of a copper IUD for EC. Exclusion Criteria: Be currently pregnant (positive high-sensitivity urine pregnancy test); Be currently breastfeeding or within 30 days of discontinuing breastfeeding, unless the subject has already had a menses following discontinuation of breastfeeding; Desire to use hormonal systemic contraception within 5 days of study drug use Have had a female sterilization procedure; Have a partner with a history of vasectomy; Current inability to tolerate oral medication; Have impaired hypothalamic-pituitary-adrenal reserve or oral glucocorticoid replacement therapy in the last year. Have known liver disease; Have known liver abnormalities with elevated enzymes at least twice the upper limit of normal requiring use of liver enzyme inducers. Have known hypersensitivity to the active substance UPA or LNG, or any of the excipients of the study treatment. Have a current need for exogenous hormones. 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; 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). 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. Have a history of a bariatric surgery procedure associated with malabsorption. Live outside of the catchment area of the study site. Have used UPA or LNG EC within 30 days prior to enrollment and not had a menses since using the drug. Be a site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: UPA 30mg<br> | Drug: Ulipristal Acetate<br>* UPA Tablet<br>* Other names: Ella;|
| Active Comparator: LNG 1.5 mg<br> | Drug: Levonorgestrel<br>* LNG Tablet<br>* Other names: Plan B;|
| Active Comparator: LNG 3.0<br> | Drug: Levonorgestrel<br>* LNG Tablet (x2)<br>* Other names: Plan B (double dose);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of pregnancies of UPA 30 mg, LNG 1.5 mg and LNG 3.0 mg in women with weight ≥ 80 kg for emergency contraception (within 72 hours of unprotected intercourse). |  | 1-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events of UPA 30 mg, LNG 1.5 mg and LNG 3.0 mg in women with weight ≥80 kg seeking emergency contraception. |  | 1-3 months |