Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||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|
- Efficacy [ Time Frame: At all visits ] [ Designated as safety issue: No ]Primary endpoint: The Pearl Index for women 35 years of age derived from using all cycles for which back up contraception is not used will be the primary efficacy endpoint. This index will be calculated for the women participating in Protocol 300 B and will then be pooled with data from women 35 years who participate in 300 A (CCN006).
- Safety [ Time Frame: At all visits ] [ Designated as safety issue: Yes ]Each subject's health status will be monitored carefully throughout the trial. Baseline data collected at the screening visit will consist of the medical and gynecologic history and physical examination findings including breast and pelvic exam (to include Pap test and STI screening for chlamydia and gonorrhea). These assessments will be repeated at the 6th cycle visit (with the exception of the Pap, and STI screening). Baseline data obtained from clinical chemistries and a CBC will be used to monitor liver and renal function, lipid levels and hematologic status.
|Study Start Date:||December 2005|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Drug: NES/EE CVR
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00263341
|United States, California|
|Women and Children's Hospital, LAC/USC Medical Center|
|Los Angeles, California, United States, 90033|
|University of California, San Francisco General Hospital, Department of Obstetrics & Gynecology|
|San Francisco, California, United States, 94110|
|United States, Illinois|
|University of Chicago Hospitals|
|Chicago, Illinois, United States, 60637|
|United States, New York|
|Montefiore Medical Center/Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|United States, Ohio|
|Columbus Center for Women's Heatlh Research|
|Columbus, Ohio, United States, 43213|
|University of Campinas, Department of Obstetrics & Gynecology|
|Campinas, Sao Paulo, Brazil|
|Instituto Chileno de Medicina Reproductiva|
|Santo Domingo, Dominican Republic|
|Family Federation of Finland|
|University of Szeged, Department of Obstetrics & Gynecology|
|Karolinska Institutet, Department of Woman and Child Health, Division of Obstetrics & Gynecology|
|Stockholm, Sweden, SE 17176|
|Study Director:||Ruth Merkatz, Ph.D.||Population Council|