EC PK in Women With Normal and Obese BMI

Phase 4

Completed

Brief Summary: A well-designed pharmacokinetics (PK) study may identify the physiologic basis for observed differences in levonorgestrel emergency contraception (LNG-EC) and ulipristal acetate emergency contraception (UPA-EC) failure rates in women with normal and obese BMI. The investigators propose a study to compare serum LNG and UPA levels after administration of a single-dose of LNG-EC or UPA-EC. The investigators hypothesize that there will be no difference in PK parameters between women with normal BMI and obese women.

Detailed Description: Eligible women will present to the division research office, at which time a history and physical exam will be completed. Each participant's BMI will be confirmed and she will be assigned to one of two BMI groups (18.5-24.9 versus 30-39.9). At the conclusion of the enrollment visit, the research coordinator will randomize each woman to receive a single-dose pill of either levonorgestrel 1.5mg (like Plan B One-Step® or its generic formulations) or ulipristal acetate 30mg (ellaOne®) on two separate occasions.

Recruitment & Eligibility

Inclusion Criteria

Women aged 18-45 years
English-speaking
BMI 18.5-24.9 kg/m2 or obese BMI 30.0-39.9 kg/m2
Regular menstrual cycles
No use of medroxyprogesterone acetate at least 6 months prior to study enrollment, unless resumption of two menstrual cycles
No use of levonorgestrel intrauterine system (levonorgestrel-IUS), etonogestrel implant or combined hormonal contraception at least one month prior to the study and resumption of one menstrual cycle
Women who are postpartum or post-abortion will be included if they have had at least one menstrual cycle since their last pregnancy

Exclusion Criteria

Prior allergic reaction to LNG-EC or UPA-EC
Use of hormonal emergency contraception within the past month
Women who are currently pregnant or who are currently breastfeeding
History of cancer other than non-melanoma skin cancer
Medical or surgical conditions or conditions requiring therapies known to impact sex steroid production or metabolism
- Use of HAART therapy for management of HIV infection
- Concomitant use of CYP3A4 inducers like rifampin, barbiturates, carbamazepine, lamotrigine, bosentan, felbamate, griseofulvin, oxcarbazepine, phenytoin, St. John's Wort and topiramate
Current participation in any other trial of an investigational medicine or device in the three months leading up to this study

Arm && Interventions

Group	Intervention	Description
Obese-BMI	LNG-EC	Women with obese BMI will receive the first emergency contraception (EC) dose and complete pharmacokinetics (PK) assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs Levonorgestrel (LNG-EC) and Ulipristal Acetate (UPA-EC) will be given in random order.
Normal-BMI	UPA-EC	Women with normal BMI will receive the first emergency contraception (EC) dose and complete pharmacokinetics (PK) assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs Levonorgestrel (LNG-EC) and Ulipristal Acetate (UPA-EC) will be given in random order.
Obese-BMI	UPA-EC	Women with obese BMI will receive the first emergency contraception (EC) dose and complete pharmacokinetics (PK) assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs Levonorgestrel (LNG-EC) and Ulipristal Acetate (UPA-EC) will be given in random order.
Normal-BMI	LNG-EC	Women with normal BMI will receive the first emergency contraception (EC) dose and complete pharmacokinetics (PK) assessments; then return to the clinic after at least 8 days to receive the second study drug and complete the same assessments. The study drugs Levonorgestrel (LNG-EC) and Ulipristal Acetate (UPA-EC) will be given in random order.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time 0 to 24 Hours of Serum UPA Concentration	Up to 24 hours	UPA-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women.
Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration	Up to 24 hours	LNG-EC PK parameter (AUC 0-24 h) in women with normal and obese BMI women.

Secondary Outcome Measures

Name	Time	Method
Elimination Half-life of Serum UPA	Up to 24 hours	(t1/2) calculated in women with normal and obese BMI
Maximum Concentration of Serum UPA	Up to 24 hours	(Cmax) calculated in women with normal and obese BMI
Clearance of Serum UPA	Up to 24 hours	(Cl) calculated in women with normal and obese BMI
Maximum Concentration of Serum LNG	Up to 24 hours	(Cmax) calculated in women with normal and obese BMI
Time to Maximum Concentration of Serum LNG	Up to 24 hours	(Tmax) calculated in women with normal and obese BMI
Time to Maximum Concentration of Serum UPA	Up to 24 hours	(Tmax) calculated in women with normal and obese BMI
Elimination Half-life of Serum LNG	Up to 24 hours	(t1/2) calculated in women with normal and obese BMI
Clearance of Serum LNG	Up to 24 hours	(Cl) calculated in women with normal and obese BMI