Clinical trial NCT05294341: Metabolism of 0.35mg Norethindrone vs 5mg Norethindrone Acetate
Official title: Pilot Study Examining the Pharmacokinetics of 0.35mg Norethindrone vs 5mg Norethindrone Acetate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Contraception
Keywords: pharmacokinetics
pilot study
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 0.35mg norethindrone, also known as progesterone only pills, are routinely prescribed as immediate postpartum oral contraception. Norethindrone acetate is prescribed for gynecologic indications, but has never been studied as an efficacious form of contraception. This is a pilot crossover study examining the pharmacokinetics of norethindrone, the metabolically active component of both drugs, in participants taking 5mg norethindrone and 0.35mg norethindrone acetate.

Detailed description: Progesterone only pills are utilized as immediate postpartum contraception. Though it is demonstrated to be safe as contraception, it is known to be less efficacious than other forms of progestin-only contraception, such as DMPA injections, etonogestrel implant insertion, or progestin-containing intrauterine devices. This is largely secondary to its short half-life. Norethindrone acetate is known to have a longer half-life than norethindrone. Though it is widely used in various gynecologic settings, it has never been studied as a contraceptive option. The metabolically active component of norethindrone is norethindrone itself. This study aims to confirm that amounts of norethindrone are comparable or greater in participants taking 5mg of norethindrone acetate vs taking 0.35mg norethindrone, thereby demonstrating the ability to prescribe 5mg norethindrone acetate as a safe and efficacious form of contraception.

This is a pilot crossover study that will study the pharmacokinetics of norethindrone vs norethindrone acetate. 6 subjects will be a part of this study. Three will be assigned to 0.35mg norethindrone as the initial drug and three will be assigned to 5 mg norethindrone acetate as the initial drug. Starting on day 1-3 of the menstrual cycle, participants will start taking Drug 1 at 7:30am every morning for Days 1-7. At 8am Day 1-7 participants will present to the the Clinical Research Laboratory at Milton S. Hershey Medical Center for an 8am blood draw to examine serum norethindrone levels. On Day 8 participants will stop taking the medication. On Day 8 subjects will present to the Clinical Research Lab and will have an IV placed. Participants will get a pregnancy test to rule-out pregnancy and then hourly blood draws from 8am to 4pm to examine serum norethindrone levels. Participants will also fill out a Symptom Diary detailing side effects and overall satisfaction with the drug.

Additionally, on Days 1 and 21, participants will have serum levels drawn to evaluate levels of luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone levels.

Participants will undergo a one month washout. For Cycle 2, the alternate drug will be administered and monitored in the process as detailed above.

The serum samples will be collected in batches, will be spun down and stored in a -4 degree freezer. Levels of norethindrone in serum samples will be measured.

Eligibility criteria: Inclusion Criteria:

1. Women aged 18-55yo
2. Menstrual length cycles 24-34 days
3. Previously on non-hormonal forms of contraception
4. Ability to follow-up routinely

Exclusion Criteria:

1. Current pregnancy
2. History of anovulatory cycles
3. Irregular cycles (PCOS)
4. On hormonal-based contraception or HRT in past 3 months
5. Infertility or active hormonal treatment of infertility in past 3 months
6. Hx of hysterectomy
7. Postpartum \<3 months
8. H/o liver disease, kidney disease, breast cancer, venous thromboembolism
9. Unwilling to use barrier contraception or abstinence
10. Inability to follow-up routinely

Primary outcomes:
measure: Serum Concentration of Norethindrone
timeFrame: Day 1-7
Secondary outcomes:
measure: Day 8 Norethindrone Levels
timeFrame: Hourly for eight hours on Day 8
measure: Differences of Serum Levels of Estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and Progesterone
timeFrame: Day 1 and Day 21
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Hershey Medical Center
state: Pennsylvania
Study officials:
References: