Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol
Condition: Contraception
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this 1-year study is to evaluate the efficacy and safety of a new
      contraceptive vaginal ring (CVR) delivering low doses of Nestorone (NES), a new,
      nonandrogenic progestin, and ethinyl estradiol (EE), an estrogen used in oral contraceptives.
      The CVR, which is made of silicone rubber, is designed to be used for 1 year (13 menstrual
      cycles) before replacement is required.
    

Detailed description: 
      The objective of this study is to evaluate the contraceptive efficacy, cycle control, and
      safety of a reusable CVR delivering low daily doses of NES and EE for a 1-year (13-cycle)
      period.

      Nestorone is a potent, nonandrogenic, 19-norprogesterone derivative, which is not active when
      given orally, but is highly active when delivered via non-oral delivery systems, such as
      CVRs, implants, or transdermal preparations. The high potency of NES makes it an excellent
      candidate for use in contraceptive delivery systems designed to be effective for prolonged
      periods. This characteristic of Nestorone has been utilized in the design of a contraceptive
      vaginal ring that releases low daily doses of both NES and EE and is effective for a 1-year
      (13-cycle) period. The NES/EE vaginal ring is a long-acting contraceptive device, but, unlike
      other long-term methods, it use is controlled by the woman without the need for medical
      intervention.

      The efficacy of NES/EE vaginal ring in preventing pregnancy during a 1-year (13-cycle) period
      will be studied in women who have regular sexual activity and use no other form of
      contraception. The Pearl index for all women (18-<40) and Kaplan-Meier life table analyses
      will be assessed for all subjects and for subjects £ 35 years and will provide supportive
      analyses for demonstrating efficacy. Pearl indices will be based on all cycles and on all
      cycles for which back-up contraception is not used.

      The number of bleeding/spotting days per cycle or reference period will be used to evaluate
      cycle control. Safety will be evaluated by regular assessments of blood pressure, pulse, and
      body weight and by laboratory testing and Pap smears at screening and termination, and by the
      frequencies of adverse events and serious adverse events. Additional safety evaluations will
      be obtained in a companion Phase 3 study conducted by the NIH (Protocol CCN006) with three
      substudies to evaluate 1) the effect of treatment on 4 hepatic proteins that may be
      associated with a risk for thromboembolism; 2) the effect of reusing the same CVR for 13
      consecutive cycles on vaginal flora and the risk of infection; and 3) the effect of vaginal
      delivery of NES and EE on the endometrium.

      A nested pharmacokinetics/pharmacodynamics/safety study is also being conducted in a subset
      of 39 patients. Blood samples are drawn during study cycles 1, 3, and 13 in order to assess
      ovulation suppression, measured by serum progesterone concentration, and the pharmacokinetics
      of NES and EE.
    

Intervention name(s): NES/EE CVR
Intervention type(s): Combination Product
Intervention description(s): This is a Phase 3, multicenter, open-label study of a 21/7-day regimen of the 150/15 NES/EE CVR, in healthy women followed on an outpatient basis up to one year (13 cycles) of treatment over one year. Because of the stop treatment date of December 31, 2008 for all participants, women enrolling or re-enrolling in 2008 may not complete a full 13 cycles of treatment. Subjects may also participate in a 6 month follow-up period after the 300B study. The ring is designed to last for 12 months.
Other intervention name(s): Nestorone (segesterone acetate) Ethinylestradiol Contraceptive Vaginal Ring
Intervention MeSH terms: Contraceptive Agents; Ethinyl Estradiol
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Contraceptive agents; Female contraception; Progestins