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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Contraception
• Intervention / Treatment: Drug: UPA-ECx1; Drug: UPA-ECx2

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.

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• 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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: UPA-ECx1 followed by ECx2; 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; Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC; Other Names: Ella; Ella-One; Drug: UPA-ECx2; Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC; Other Names: ella; ella-one
Experimental: UPA-ECx2 followed by ECx1; 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; Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC; Other Names: Ella; Ella-One; Drug: UPA-ECx2; Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 60mg of UPA-based EC; Other Names: ella; ella-one
Other: UPA-ECx1 Normal BMI/weight; 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; Evaluating the pharmacodynamic and pharmacokinetic outcomes in obese women using 30mg of UPA-based EC; Other Names: Ella; Ella-One

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Delay in Follicular Rupture Beyond 5 Days	Follicular rupture (yes/no) beyond 5 days from EC dosing by ultrasound in participants with a BMI >/=30 kg/m2. The comparison is between menstrual cycles where 30 versus 60 mg of UPA was taken. Follicular rupture is defined as the disappearance of or >50% reduction in size of the leading follicle. The day of EC dosing is defined as day zero.	1 menstrual cycle, assessed up to 38 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration of Ulipristal Acetate	Maximum serum concentration (Cmax) of UPA in participants with BMI >/=30 kg/m2 with 30 mg UPA, with BMI >/= 30 kg/m2 with 60 mg UPA, and normal BMI participants with 30mg UPA	24 hours

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

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2017
• Primary Completion (Actual): January 13, 2022
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: January 14, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: obesity; emergency contraception; BMI; body weight; ulipristal acetate; levonorgestrel
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: OHSU IRB 016291

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 our purposes; with local colleagues at seminars and talks including our 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
• product manufactured in and exported from the U.S.: No