EC PK in Women With Normal and Obese BMI

Pharmacokinetics of Levonorgestrel and Ulipristal Acetate Emergency Contraception in Women With Normal and Obese Body Mass Index

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: LNG-EC; Drug: UPA-EC

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Normal-BMI; 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.	Drug: LNG-EC; FDA-approved emergency contraceptive pill containing levonorgestrel 1.5mg; Other Names: Next Choice One Dose; Levonorgestrel (LNG) emergency contraceptive (EC); Drug: UPA-EC; FDA-approved emergency contraceptive pill containing ulipristal acetate 30mg; Other Names: Ulipristal acetate (UPA) emergency contraceptive (EC); ella
Other: Obese-BMI; 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.	Drug: LNG-EC; FDA-approved emergency contraceptive pill containing levonorgestrel 1.5mg; Other Names: Next Choice One Dose; Levonorgestrel (LNG) emergency contraceptive (EC); Drug: UPA-EC; FDA-approved emergency contraceptive pill containing ulipristal acetate 30mg; Other Names: Ulipristal acetate (UPA) emergency contraceptive (EC); ella

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Carolyn L Westhoff, MD, Director, Division of Family Planning and Preventive Services; Study Director: Piyapa Praditpan, MD, Clinical instructor, Division of Family Planning and Preventive Services

Publications and helpful links

General Publications

• Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, Gainer E, Ulmann A. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011 Oct;84(4):363-7. doi: 10.1016/j.contraception.2011.02.009. Epub 2011 Apr 2.
• Kapp N, Abitbol JL, Mathe H, Scherrer B, Guillard H, Gainer E, Ulmann A. Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception. Contraception. 2015 Feb;91(2):97-104. doi: 10.1016/j.contraception.2014.11.001. Epub 2014 Nov 8.
• Gemzell-Danielsson K, Kardos L, von Hertzen H. Impact of bodyweight/body mass index on the effectiveness of emergency contraception with levonorgestrel: a pooled-analysis of three randomized controlled trials. Curr Med Res Opin. 2015 Dec;31(12):2241-8. doi: 10.1185/03007995.2015.1094455. Epub 2015 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2015
• Primary Completion (Actual): December 29, 2015
• Study Completion (Actual): February 3, 2017

Study Registration Dates

• First Submitted: February 16, 2016
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: June 30, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Emergency contraception
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel; Contraceptive Agents; Ulipristal acetate; Contraceptives, Postcoital
• Other Study ID Numbers: AAAP1857

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Publication
   Information comments: Results Reference: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No