Drospirenone-only Pill as Emergency Contraception

Drospirenone for Emergency Contraception: a Dose-finding Pilot Study

Emergency contraception (EC) provides an additional measure to help prevent pregnancy after unprotected intercourse or contraceptive failure. The two currently available oral emergency contraceptive methods, levonorgestrel (LNG) and ulipristal acetate (UPA), have differing availability and effectiveness. Overweight and obesity are strong risk factors for failure of EC containing LNG and UPA for body mass index (BMI) ≥ 26kg/m2 and ≥35kg/m2, respectively, resulting in limited EC options for much of the population. Drospirenone is a unique progestin that effectively inhibits ovulation when taken daily as progestin-only oral contraception and has pharmacokinetic properties that make it a good candidate for a novel effective emergency contraceptive method across BMI categories.

The investigators propose a dose-finding, adaptive-design pilot study evaluating if a single dose of drospirenone can inhibit ovulation prior to the luteinizing hormone (LH) surge. The dose-finding study design will be conducted in a well-established 3+3 model with 2 planned study arms stratified by BMI. The investigators hypothesize that a single dose of drospirenone will effectively inhibit ovulation when administered prior to the LH surge. This pilot data will directly support the dose selection for future research further evaluating the efficacy of drospirenone-only EC aimed at ultimately increasing oral EC options, particularly for patients with overweight or obesity.

Study Overview

• Status: Not yet recruiting
• Conditions: Contraception
• Intervention / Treatment: Drug: Drospirenone-only pill

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paige Kendall, MD; Phone Number: 303-724-2019; Email: paige.kendall@cuanschutz.edu
• Study Contact Backup: Name: Eva Dindinger, MPH; Email: eva.dindinger@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
      • Contact: Eva Dindinger; Email: eva.dindinger@cuanschutz.edu
      • Principal Investigator: Paige Kendall, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Overall good general health.
2. Age 18-35 years at time of enrollment.

3. BMI

   1. Initial dose-finding cohort: BMI < 30 kg/m2; thereafter no BMI limit

4. Intact uterus with at least 1 ovary.

5. Regular menstrual cycles that occur every 21-35 days:

   1. If patient is postpartum or post-second trimester abortion, she must have 3 menses (2 cycles) prior to enrollment.
   2. If patient had a first trimester abortion or pregnancy loss, she must have one spontaneous menses prior to enrollment.
6. Negative urine pregnancy test at screening visit and at time of drospirenone administration.
7. Consistent use of a barrier method or other non-hormonal birth control method throughout the study, or otherwise not at risk for pregnancy.
8. Ovulatory as confirmed by a documented screening progesterone (P4) level ≥3ng/ml at screening visit.
9. Willingness and ability to abstain from medications and supplements known to induce/inhibit CYP3A4 during the study period
10. Willingness and ability to comply with the protocol requirements.
11. Lives within the study site catchment area or within a reasonable distance from the site.

Exclusion Criteria:

1. Have a known hypersensitivity or contraindications to drospirenone.
2. Currently taking any known CYP3A4 inducers/inhibitors.
3. Medical conditions that affect liver function (e.g., hepatitis, cirrhosis; assessed via participant self-report).
4. Medical conditions that affect kidney function (e.g., chronic kidney disease, primary renal disease; assessed via participant self-report) or use of medications that can affect kidney function and/or electrolyte balance (e.g., ACE inhibitors, diuretic medications; assessed via participant self-report).
5. A known history of or presence of hyperkalemia (potassium ≥4.5mEq/L) or renal impairment (creatinine of ≥1.1mg/dL) at screening visit.
6. Known or suspected current alcohol dependence syndrome or any illicit drug use that may affect the metabolism of the drospirenone.
7. Undiagnosed abnormal uterine/genital bleeding.
8. Uncontrolled thyroid disorder.
9. Use of long-acting injectable hormonal contraceptive within the past 6 months prior to enrollment unless the patient has had at least one spontaneous menstrual cycle since the last injection.
10. Recent use of hormonal oral, patch, intravaginal, or intrauterine contraception unless that patient has had at least one spontaneous menstrual cycle since discontinuation.
11. Currently breastfeeding or are within 30 days of discontinuing breastfeeding unless the patient has already had a menses following discontinuation.
12. Planning on undergoing major surgery during study participation.
13. Planning significant weight loss during the study related to bariatric surgery, dieting, or other causes.
14. Planning pregnancy during their anticipated months of study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose finding; Drospirenone-only pill single-dose ranging from 16mg to 32mg	Drug: Drospirenone-only pill; Single dose based on adaptive dose-finding design
Experimental: Primary ovulation inhibition testing; Drospirenone-only pill single-dose at dose determined by dose finding arm	Drug: Drospirenone-only pill; Single dose based on adaptive dose-finding design

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum progesterone concentration	Serum progesterone concentration measured after drug administration	Measured daily for the seven days immediately following administration of the drospirenone-only pill dose during the Intervention cycle (each cycle is 21-35 days)
Dominant ovarian follicle ultrasound measurement	Measurement of the dominant ovarian follicle in three planes (width, length, height) using transvaginal ultrasound	Measured daily for the seven days immediately following administration of the drospirenone-only pill dose during the Intervention cycle (cycle length 21-35 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum potassium concentration	Measured as a safety outcome	Measured on the first and second days immediately following administration of the drospirenone-only pill dose during the Intervention cycle (cycle length 21-35 days)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Estimate): January 9, 2023

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: emergency contraception; drospirenone
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Drospirenone
• Other Study ID Numbers: 22-2178

Plan for Individual participant data (IPD)

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

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