Effectiveness of Orally Dosed Emergency Contraception in Obese Women - UPA

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. Our 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. More data is needed regarding emergency contraception containing ulipristal acetate. The overall project will be focused on both levonorgestrel (LNG) - and ulipristal acetate (UPA)-containing emergency contraception but this protocol registration is for the UPA 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. Our preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed EC in obese women. We hypothesize 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, we plan to perform detailed pharmacokinetic and pharmacodynamic studies of UPA-based EC in obese women and expand upon our preliminary findings of LNG-based EC. This protocol registration is for the UPA aspect of the study procedures focused on the pharmacokinetics and pharmacodynamics of UPA and will include a dose escalation intervention.

Official Title
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Improving the Effectiveness of Orally Dosed Emergency Contraceptives in Obese Women - PK and PD of 30mg and 60mg UPA

Conditions
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Obesity, Contraception

Intervention / Treatment
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* Drug: UPA-ECx1
* Drug: UPA-ECx2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy women Aged 18-35 years old Regular menses (every 21-35 days) experiencing an ovulatory screening cycle with a progesterone level of 3 ng/mL or greater Subjects must have a BMI of >30kg/m2 and weight at least 80kg or more OR a BMI <25kg/m2 and a weight of less than 80kg. 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: UPA-ECx1 followed by ECx2<br>Ulipristal acetate 30mg orally x 1 dose, washout cycle and then in the next menstrual cycle, 60mg x 1 dose. Timing of dosage depends on follicle measurements. | Drug: UPA-ECx1<br>* Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC<br>* Other names: Ella-One;Drug: UPA-ECx2<br>* Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC<br>* Other names: ella-one;|
| Experimental: UPA-ECx2 followed by ECx1<br>Ulipristal acetate 60mg orally x 1 dose, washout cycle, and then in next menstrual cycle 30mg orally x 1 dose. Timing of dosage depends on follicle measurements. | Drug: UPA-ECx1<br>* Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC<br>* Other names: Ella-One;Drug: UPA-ECx2<br>* Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC<br>* Other names: ella-one;|
| Other: UPA-ECx1 Normal BMI/weight<br>Ulipristal acetate 30mg orally x 1 dose. timing of dosage depends on follicle measurements. This is to obtain a normal BMI control group. | Drug: UPA-ECx1<br>* Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC<br>* Other names: Ella-One;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay in follicular rupture | Follicular rupture (yes/no) by ultrasound between treatment groups (30 vs 60 mg of UPA). Defined as the disappearance of or >50% reduction in size of the leading follicle | 1 menstrual cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration | Maximum serum concentration (Cmax) of obese users of 30 versus 60 mg of UPA and between obese and normal BMI users of 30mg UPA | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, body weight, BMI, emergency contraception, levonorgestrel, ulipristal acetate