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Progestin eyed for use in contraceptive gel
Your next patient is a 17-year-old female who is seeking contraception for pregnancy prevention. She is not sure if she wants to take the Pill, and says she's leery of wearing a contraceptive patch. What options can you offer her?
Research scientists are making plans to study a contraceptive gel that could be applied on the arm or the abdomen. Antares Pharma, an Exton, PA-based company, and the New York City-based Population Council have announced plans to develop contraceptive products containing the council's patented progestin, Nestorone, in Antares's proprietary Advanced Transdermal Delivery gel platform. The two organizations expect the first clinical study in women to start in 2007.
Nestorone is a very potent antiovulatory agent; very small doses are needed to be able to block ovulation, says Regine Sitruk-Ware, MD, executive director of research and development at the Population Council. This capability makes Nestorone ideal to use in delivery systems such as rings, implants, or transdermal gels or sprays, where only small amounts of product can be delivered, she notes.
Antares Pharma's Advanced Transdermal Delivery system is a clear and cosmetically acceptable drug delivery gel. Within a few minutes of application to the skin, an invisible depot is formed within the epidermis, allowing the drug to be slowly absorbed into systemic circulation. If the Nestorone gel formulation proves safe and effective, it may offer a discreet option to the contraceptive patch (Ortho Evra, Ortho-McNeil Pharmaceutical, Raritan, NJ), since women will not be "labeled" with a patch on their skin, says Stephanie Baldwin, an Antares Pharma spokes-woman. Systemic adverse events should be minimized as hepatic first-pass metabolism will be eliminated via the transdermal route of administration in comparison to oral contraceptive products, she notes.
Spray and ring eyed
Nestorone is but one of several new progestins synthesized in the last two decades; other progestins include dienogest, drospirenone, nomegestrol acetate and trimegestone. The new progestins are designed to have no androgenic or estrogenic actions and to be closer in activity to progesterone.1 Clinicians in the United States are most familiar with drospirenone, which is used in the oral contraceptives, Yasmin and Yaz, from Berlex in Montville, NJ.
The Population Council is in partnership with Acrux, a Melbourne, Australia, pharmaceutical company, to develop a Nestorone contraceptive spray.
Preliminary results from two Phase I studies with the spray showed that the progestin was well absorbed and reached in the blood levels well within the range targeted for blocking ovulation, reports Sitruk-Ware. The council is preparing for a Phase II study in which scientists will test the formulation to confirm its action on ovulation inhibition, she notes.
The Population Council also is moving forward with research on a Nestorone contraceptive vaginal ring. A multicenter one-year dose-finding trial looked at three dose combinations of Nestorone and ethinyl estradiol in a ring delivery system to study its effectiveness, safety, and acceptability. Results indicate that the studied formulations, used on a 21-day-in and seven-day-out regimen, provided women safe and effective contraception.2
Results from a just-published study indicate that a Nestorone contraceptive vaginal ring should be as safe as a combined oral contraceptive when it comes to thrombosis risk.3 Scientists compared use of a vaginal ring with 150 mcg of Nestorone and 15 mcg ethinyl estradiol against an oral contraceptive (Stediril 30, 30 mcg ethinyl estradiol and 15 mcg levonorgestrel; Wyeth Pharmaceuticals, Collegeville, PA). The study included 45 women who were randomly assigned to use one of the drugs for 77 days.
The next step in research will include a large-scale Phase 3 study, using manufactured rings. The council is working with a contract manufacturer, QPharma, Malmö, Sweden, to make the devices. Since Phase II tests were carried out with rings manufactured at the council's Center for Biomedical Research, further tests will need to be carried out to evaluate the effectiveness and side effects of the mass-manufactured ring, as well as a pharmacokinetic trial designed to determine the amount of Nestorone taken up into the bloodstream with use of the ring over a course of three cycles.
According to the Population Council, the Phase III study will run until late 2008. Study results will form the basis of an application to the Food and Drug Administration for possible U.S. approval.