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.

Condition	Intervention	Phase
Contraception	Drug: NES/EE CVR	Phase III

Further study details as provided by Population Council:

Expected Total Enrollment:  1280

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 cumulative pregnancy rate and the Pearl index after 1 year of use will be used to evaluate efficacy. 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. Adverse events will be recorded throughout the study.

A nested pharmacokinetics/pharmacodynamics/safety study will be conducted in a subset of 39 patients. Blood samples will be 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.

Ages Eligible for Study:  18 Years   -   38 Years,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Healthy women who meet the following criteria:

  • are aged 18-38 years, do not intend to become pregnant during the study period, are sexually active, and wish to use a non-oral contraceptive
  • have a history of 3 regular menstrual cycles of 28 ± 7 days or, if postpartum or postabortal, have a history of 1 regular cycle of 28 ± 7 days and have had at least 1 cycle (2 menses) with a cycle length consistent with past
  • have an intact uterus and both ovaries
  • are able and willing to comply with the protocol
  • are able and willing to give informed consent [for pharmacokinetics study only]
  • are willing to undergo frequent blooding sampling]

Exclusion Criteria:

• Exclusion criteria are similar to those in studies with oral contraceptives. Women who meet any of the following criteria will be excluded:

  • Known hypersensitivity to estrogens or progestins
  • Undiagnosed vaginal discharge or vaginal lesions or abnormalities
  • Smoking more than15 cigarettes per day if >=35 years*Breastfeeding
  • Current or past thrombophlebitis or thromboembolic disorders
  • Cerebrovascular or coronary artery disease
  • Carcinoma (hormone dependent tumor or other evolutive carcinoma)
  • Medically diagnosed severe depression
  • Headaches with focal neurological symptoms
  • Undiagnosed abnormal genital bleeding
  • Cholestatic jaundice of pregnancy or jaundice with prior steroid use
  • Benign or malignant liver tumors; active liver disease
  • Diastolic BP ≥85 mm and systolic BP ≥135 mmHg after 5 min. rest
  • Known or suspected alcoholism or drug abuse
  • Abnormal serum chemistry values according to the physician’s judgment *Participation in another clinical trial
  • Weight > 90 kg (198 lb)
  • Use of enzyme inducers on a regular basis
  • Use of combined injectable contraceptives during the previous 2 months (eg, cyclofem) or 6 months (eg, DMPA); use of oral contraceptives within 1 month of study entry; use of implanted hormonal contraceptives within 1 month of study entry
  • Known hypersensitivity to silicone rubber
  • Cystoceles or rectoceles or other anatomic abnormality precluding use of a CVR
  • Women at high risk of contracting HIV infection

Please refer to this study by ClinicalTrials.gov identifier  NCT00263341

Ruth Merkatz, Ph.D.      212-327-8647    rmerkatz@popcouncil.org

California
      Women and Children''''s Hospital, LAC/USC Medical Center, Los Angeles,  California,  90033,  United States
Chile
      Instituto Chileno de Medicina Reproductiva, Santiago,  Chile
Dominican Republic
      PROFAMILIA, Santo Domingo,  Dominican Republic

Study chairs or principal investigators

Ruth Merkatz, Ph.D.,  Study Director,  Population Council   

Study ID Numbers:  Protocol 300
Last Updated:  December 8, 2005
Record first received:  December 6, 2005
ClinicalTrials.gov Identifier:  NCT00263341
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10