A Dose-finding Study to Evaluate the Effect of a Contraceptive Vaginal Ring, Releasing Nestorone® and Estradiol, on Cycle Control, Ovulation Inhibition, and Pharmacokinetics in Normal Cycling Women

Inclusion Criteria

Women who meet all the following criteria are eligible for enrollment in the trial:

• Healthy women of reproductive age (18-39 years, inclusive, at the enrollment visit).
• Have a regular menstrual cycle that is 21-35 days in duration.
• Have intact uterus and both ovaries.
• Will be able and willing to comply with the protocol and sign an informed consent.
• Will not be at risk for pregnancy. They will be consistently using a non-hormonal method, have a surgically sterile male partner with a vasectomy, be abstinent, or be in a same-sex relationship from the control period through study exit (including recovery period).
• Will have diastolic blood pressure (BP) ≤85 mm Hg and systolic BP ≤135 mm Hg after 5 minutes in sitting position.
• Willing to abstain from use of non-water based vaginal lubricant during the study.

Exclusion Criteria

Women who meet any of the following criteria are not eligible for enrollment in the trial:

• Participating in another clinical trial involving an investigational product within the last 30 days (prior to screening) or planning to participate in another clinical trial during this study.
• Not living in the catchment area of the clinic.
• Known hypersensitivity to progestins or estrogen.
• All contraindications to combined estrogen-progestin contraceptive use including:
• Thrombophlebitis or thromboembolic disorders.
• Past personal history of deep vein thrombophlebitis or thromboembolic disorders.
• History of venous thrombosis or embolism in a first-degree relative 35.
• Use of injectable contraceptives (e.g. cyclofem or depo-medroxyprogesterone acetate) during the 6 months prior to enrollment or no spontaneous menses since last injection.
• Use of oral contraceptives within one month prior to start of control cycle (subjects must undergo informed consent process and screening procedures before stopping oral contraceptives to participate in the study).
• Use of hormonal contraceptives. NOTE: Removal of implanted hormonal contraceptives must have been for personal reasons unrelated to the purpose of enrollment in this study.
• Current use of an intrauterine device (IUD). NOTE: Removal of an IUD must have been for personal reasons unrelated to the purpose of enrollment in this study.
• Known hypersensitivity to silicone rubber.
• History of toxic shock syndrome.
• Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a vaginal ring.
• Planning to undergo major surgery during the study.
• Severe constipation.
• Use of liver enzyme inducers or inhibitors on a regular basis.
• Known HIV infection.
• Bariatric surgery within the past year prior to enrollment.
• Any abnormalities found during the transvaginal ultrasound (TVUS) that the PI or medically qualified sub-investigator deems to put the subject at risk.
• Have issues or concerns (in the judgment of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.