Metabolism of 0.35mg Norethindrone vs 5mg Norethindrone Acetate
Condition: Contraception
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Norethindrone Acetate 5 MG; Norethindrone 0.35 MG
Intervention type(s): Drug; Drug
Intervention description(s): As specified in arm design; As specified in arm design
Intervention MeSH terms: Norethindrone; Norethindrone Acetate
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: pharmacokinetics; pilot study