NCT00263341

Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol

A Multicenter, Open-label Study on the Efficacy, Cycle Control and Safety of a Contraceptive Vaginal Ring Delivering a Daily Dose of 150 ug of Nestorone® and 15 ug of Ethinyl Estradiol

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,135 (actual)
• Sponsor: Population Council · Academic / Other
• Sex: Female
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Conditions

• Contraception

Interventions

Type	Name	Description
COMBINATION_PRODUCT	NES/EE CVR	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.

Timeline

• Start date: 2005-12-01
• Primary completion: 2014-08-01
• Completion: 2014-08-01
• First posted: 2005-12-08
• Last updated: 2017-10-06

Locations

12 sites across 8 countries: United States, Australia, Brazil, Chile, Dominican Republic, Finland, Hungary, Sweden