PROJECT
One-year Combination Vaginal Ring, Phase 2 Study

This project is formally titled "Nestorone®/Ethinyl Estradiol Vaginal Ring."

The NES/EE vaginal ring.

A series of Phase 2 studies have been completed to determine the appropriate dose and use regimen for the development of a contraceptive ring releasing Nestorone^® (NES, a progestin) and ethinyl estradiol (EE, a form of estrogen). These studies were carried out using rings manufactured in research laboratories at the Population Council’s Center for Biomedical Research.

Information about the current Phase 3 study is available here.

For contraception, the ring works like other hormonal methods, such as the pill, by inhibiting ovulation to prevent fertilization. In addition, the estrogen component helps maintain regular menstrual bleeding. After several multicenter studies examining dosage ratios and schedule variations, scientists are reassured of the efficacy and safety of this device.

Council scientists decided to develop a ring that releases NES/EE in a dose of 150/15 µg per day on a three-weeks-in, one-week-out usage schedule. (The ring is inserted for three weeks, then removed for one week to allow menstruation.) In order to register a product with the US Food and Drug Administration, a large-scale Phase 3 study must be carried out with rings made using a mass-manufacturing method. Consequently, a contract manufacturer (QPharma, Malmö, Sweden) has been identified to make the rings.

Two major efforts have occurred. First, the contract manufacturer has developed a manufacturing method to mass produce the rings required for the Phase 3 study. The rings were produced by the contract manufacturer and analyzed in Council laboratories to ensure that they release the proper dose of drugs. Second, a Phase 3 study of the ring is well underway to more precisely evaluate the effectiveness and side effects of the mass-manufactured ring. Over 2,000 women have been enrolled, and the treatment portion of the trial is scheduled for completion by the end of December 2008.

The rings used in the original Phase 2 dose-ranging and schedule variation studies were fabricated at the Center for Biomedical Research using different materials and different sources of materials than will be used in the mass-manufactured rings for the Phase 3 trial. For this reason, a pharmacokinetic (PK) trial is required as a nested study within the pivotal Phase 3 clinical trial. The goal of the nested PK study is to determine the amount of Nestorone taken up into the bloodstream with use of the ring over a course of three cycles.

Three clinics will participate in the nested PK study, with an additional 13 clinics coming on stream in mid-2006. A total of 1,280 women will use the ring for one year, and the study will run until late 2008. Study results will form the basis of an application to the US Food and Drug Administration for approval of the drug, which will lead to its registration and introduction into family planning programs.

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Population Council researchers

Ruth Merkatz, Narender Kumar, Frederick Schmidt, Régine Sitruk-Ware, Bruce Variano

Non-Council collaborators

Vivian Brache (Dominican Association for the Well-Being of the Family)

Horacio B. Croxatto (Chilean Institute for Reproductive Medicine)

Daniel R. Mishell (Women’s and Children’s Hospital, LA County/USC Medical Center)

Donors

The Lita Annenberg Hazen Foundation

The George J. Hecht Fund

The William and Flora Hewlett Foundation

US Agency for International Development

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