Effectiveness of Orally Dosed Emergency Contraception in Obese Women - LNG

Study Overview
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Brief Summary
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Obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed emergency contraceptives. The PI's preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed emergency contraceptives in obese women. The overall project will be focused on both levonorgestrel (LNG) - and ulipristal acetate-containing emergency contraception but this protocol registration is for the LNG aspect of the study procedures.

Detailed Description
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Emergency contraception (EC) provides a woman with an additional line of defense against unintended pregnancy following an act of unprotected intercourse. Orally-dosed EC works by delaying ovulation and reduces the risk of pregnancy for a single act of unprotected intercourse by 50-70%. Unfortunately, obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed EC and in some instances EC is equivalent to placebo. The PI's preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed EC in obese women. The hypothesis is that increasing the dose of orally-dosed EC agents will normalize the pharmacokinetics resulting in the expected treatment effect (delay in follicle rupture) in obese women. In the overall proposal, the investigators plan to perform detailed pharmacokinetic and pharmacodynamic studies of ulipristal acetate-based EC in obese women and expand upon the preliminary findings of levonorgestrel-based EC. This protocol registration is for the LNG aspect of the study procedures focused on the pharmacodynamics of LNG dose escalation

Official Title
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Improving the Effectiveness of Orally Dosed Emergency Contraceptives in Obese Women - Pharmacodynamics of 3.0mg LNG

Conditions
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Obesity

Intervention / Treatment
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* Drug: Levonorgestrel-based emergency contraception 1.5 mg
* Drug: Levonorgestrel-based emergency contraception 3.0mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally health women Aged 18-35 years old Regular menses (every 21-35 days) experiencing an ovulatory screening cycle with a progesterone level of 3ng/ml or greater. Subjects must have a BMI of >30 kg/m2 and weigh at least 80 kg or more. Exclusion Criteria: Metabolic disorders including uncontrolled thyroid dysfunction and Polycystic Ovarian Syndrome Impaired liver or renal function Actively seeking or involved in a weight loss program (must be weight stable) pregnancy, breastfeeding, or seeking pregnancy Recent (within last 8 weeks) use of hormonal contraception Current use of drugs that interfere with metabolism of sex steroids Smokers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LNG-ECx1<br>Levonorgestrel 1.5 mg orally x 1 dose. Timing of dosage depends on ovarian follicle measurements. | Drug: Levonorgestrel-based emergency contraception 1.5 mg<br>* Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC<br>* Other names: Next Choice;|
| Experimental: LNG-ECx2<br>Levonorgestrel 3mg orally x 1 dose. Timing of dosage depends on ovarian follicle measurements. | Drug: Levonorgestrel-based emergency contraception 3.0mg<br>* Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants in Two Treatment Groups (1.5mg Levonorgestrel and 3mg Levonorgestrel) With no Follicle Rupture at 5 Days Within One Menstrual (Treatment) Cycle. | No evidence of follicle rupture achieved by participant in one menstrual (treatment) cycle at 5 days post LNG dosing. Follicle rupture is defined as the disappearance of or >50% reduction in the size of the leading follicle. Dosing occurred after a dominant follicle measuring 15 mm or greater in at least one dimension was visualized on ultrasound. | 5 days post-LNG dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Follicle Rupture Before 5 Days | Among the participants with follicle rupture before 5 days, the time to rupture was measured and reported for each day up to day 5. If the date of follicle rupture was unclear by ultrasonographic imaging (eg, collapse was seen, but reduction of size was less than 50%), serum hormone levels were used to adjudicate day of ruptures. | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Body weight, Emergency contraception, Levonogestrel, Ulipristal acetate