Effectiveness of Orally Dosed Emergency Contraception in Obese Women - LNG (EC-Obesity)

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Levonorgestrel-based emergency contraception 1.5 mg; Drug: Levonorgestrel-based emergency contraception 3.0mg

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Alison Edelman, MD, MPH, Oregon Health and Science University

Publications and helpful links

General Publications

• Edelman AB, Cherala G, Blue SW, Erikson DW, Jensen JT. Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. Contraception. 2016 Jul;94(1):52-7. doi: 10.1016/j.contraception.2016.03.006. Epub 2016 Mar 18.
• Edelman AB, Hennebold JD, Bond K, Lim JY, Cherala G, Archer DF, Jensen JT. Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial. Obstet Gynecol. 2022 Jul 1;140(1):48-54. doi: 10.1097/AOG.0000000000004717. Epub 2022 Jun 7.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): January 16, 2021
• Study Completion (Actual): August 16, 2021

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimated): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Body weight; Emergency contraception; Ulipristal acetate; Levonogestrel
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: OHSU IRB 16291

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

PI acknowledges willingness to share data and materials with other investigators through established means. Data will be shared with collaborators as soon as available; with other scientists before publication if the work to be done is different from the PI's purposes; with local colleagues at seminars and talks including the yearly university-wide research-in-progress seminar; and with the scientific community at large by posters and presentations at local, regional, national, and international scientific meetings. Data will be presented via publication to the widest audience possible.

Transfer of resources is subject to the acceptance of a Materials Transfer Agreement as required by policy at OHSU.

OHSU complies with NIH policy on Sharing Research Data and on Sharing Model Organisms.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No