Research to examine new contraceptive gel
When it comes to current methods of delivery of hormonal contraception, women now can choose among pill, patch, ring, implant, and intrauterine forms of birth control. Another option is being explored. Antares Pharma, of Ewing, NJ, and the New York City-based Population Council, an international, nonprofit research organization, are moving forward with a Phase II trial of a contraceptive advanced transdermal delivery (ATD) gel.
The gel now under scientific review contains Nestorone, a progestin developed by the Population Council, and estradiol. During its research of Nestorone, Population Council scientists discovered that when it is orally ingested, the body rapidly inactivates it. Since the drug remains active when applied to the skin, the council partnered with Antares Pharma to use its patented gel system, a clear and cosmetically acceptable drug delivery gel. After the gel is applied to a woman's arm, leg, or abdomen, the drug is slowly absorbed across the skin into the systemic circulation.
One other drug on the market uses the ADT technology, says Paul Wotton, PhD, Antares Pharma's CEO. It is Elestrin, an estradiol gel from BioSante Pharmaceuticals of Lincolnshire, IL. Approved by the Food and Drug Administration in 2006 for the treatment of hot flashes, Elestrin uses a metered-dose applicator to deliver 12.5 mcg estradiol.
The Phase II trial of the Nestorone contraceptive gel will determine the lowest safe and effective dose to suppress ovulation. Three active strengths of the combination gel will be examined in 18 healthy, ovulating women. At different times during the study, each woman will receive different dosages, with appropriate washout periods between applications.
In conducting the Phase I study, scientists identified an effective dose of Nestorone and estradiol that would consistently result in blood levels that would be expected to provide effective contraception, as well as maintain a woman's normal estrogen levels and bleeding patterns.
"We believe this new formulation combining Nestorone and estradiol is likely to achieve a very high inhibition of ovulation, and has the potential to become a safe and effective contraceptive that would be easy to use and convenient for women," says Regine Sitruk-Ware, MD, executive director of research and development at the Population Council.
The Population Council continues to look at other delivery options of Nestorone, says Sitruk-Ware. The most advanced in the research pipeline is a vaginal ring, which combines the progestin with ethinyl estradiol. Researchers concluded a Phase III trial in December 2008, she notes. Earlier research indicates the ring, used on a 21-day-in and seven-day-out regimen, provided women safe and effective contraception.1
Council scientists also are studying use of Nestorone in subdermal implants for use in breast-feeding mothers, she reports.
While Nestorone is quite potent when given by nonoral routes, it is destroyed very quickly when it is taken orally, explains Sitruk-Ware. If any small quantity of the drug gets to the milk of the mother who is breast-feeding and is then ingested by the infant, it is destroyed and therefore does not affect the infant, says Sitruk-Ware. This characteristic would be an advantage in providing postpartum contraception, she notes.
The Population Council is in partnership with Acrux, a Melbourne, Australia, pharmaceutical company, to develop a Nestorone contraceptive spray.
An early pharmacokinetic trial of the transdermal steroid delivery system indicates the spray system has the feasibility of achieving serum levels of Nestorone sufficient to block ovulation and potentially provide effective contraception.2
What are some of the qualities of Nestorone that may make it suitable for contraceptive use? "One of them is that it is extremely active," Sitruk-Ware says. "It is one of the most potent for ovulation suppression, compared to other progestins, so we can use a very small dose in a delivery system, like a gel, a spray, or the vaginal ring."
The progestin does not exhibit androgenic properties, notes Sitruk-Ware. This yields an advantage in terms of tolerability.3 Women could use the drug without developing acne or oily skin, and it would not affect the lipid profile, she states.
References
- Sivin I, Mishell DR Jr., Alvarez F, et al. Contraceptive vaginal rings releasing Nestorone and ethinyl estradiol: A 1-year dose-finding trial. Contraception 2005; 71:122-129.
- Fraser IS, Weisberg E, Kumar N, et al. An initial pharmacokinetic study with a Metered Dose Transdermal System for delivery of the progestogen Nestorone as a possible future contraceptive. Contraception 2007; 76:432-438.
- Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 2006; 12:169-178.
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