Phase I trial enrolls six women
A spray-on birth control method for women recently has entered a Phase I clinical trial in which six women in Sydney, Australia, are using the new product as part of a study to determine whether the transdermal contraceptive can be used in spray formulation effectively.
Named Nestorone Metered Dose Transdermal System, the fourth-generation progestin is being studied through a joint development agreement between the Population Council of New York City and Acrux, a pharmaceutical company of Melbourne, Australia. FemPharm, a wholly owned subsidiary of Acrux, is the study’s sponsor.
Nestorone has strong progestational activity and antiovulatory potency, but it has no androgenic or estrogenic activity in vivo, which makes it suitable for contraception use.1 Since it is very potent, it can be delivered via long-term delivery systems, such as vaginal rings, implants, and transdermal system.1
"This is only a beginning of clinical trials to see if Nestorone could be used in spray formulation to deliver the Nestorone progestin in sufficient amounts to be effective," says Regine Sitruk-Ware, MD, executive director of product research and development for the Center for Biomedical Research at the Population Council in New York City.
"The Phase I trial under way is also to define how the hormone behaves in the circulating blood," she reports.
The trial involves six postmenopausal, healthy women because investigators don’t want to interfere with the cycle of ovulatory women at this early stage in which they are studying the kinetics of the product, Sitruk-Ware adds.
The contraceptive works this way: The delivery system is placed gently against the skin and depressed, which releases a light spray that quickly dries on the skin, she explains.
Then the delivery system uses an enhancer, which is patented, and the rapid drying formulation of the drug and enhancer on the skin effectively form a reservoir within the skin from which the drug slowly is absorbed into the circulation over time, Sitruk-Ware says.
"The drug is filled into a glass bottle and closed with a manual pump-metering valve," Sitruk-Ware adds. "A once-a-day application typically delivers consistent amounts through the skin to the blood stream."
No dropouts or adverse events were reported among the six volunteers as of the end of December. The trial will be completed in the first quarter of 2005, reports Sushma Kumar, PhD, senior clinical research associate with the Center for Biomedical Research at the Population Council.
The next clinical trial will be designed based on the results from this one, and the location of the new trial has not yet been determined, she says.
So far, none of the nestorone containing contraceptives has reached the market, although several new delivery systems have made it to market. "Many clinical trials using vaginal rings, implants, and gel have been completed in 2,000 women," Kumar explains.
Nestorone has been found to be safe in clinical trials, she notes. For example, vaginal rings used to deliver contraceptive hormones, such as nestorone, have shown few side effects and good control of menstrual bleeding.2 The possible side effects are typical of hormonal contraceptive methods and include headache, acne, dizziness, depression, nervousness, breast soreness, nausea, and bleeding/spotting, she notes.
"Although we have not observed any local side effects, there may be possible skin irritation at the site where the Nestorone is sprayed," Kumar says.
A direct comparison of spray-on administration could be made with transdermal patches, she adds.
"Although about 5% to 10% of the subjects using transdermal patches can experience skin irritation due to the fact that the skin is covered with an occlusive system for seven days, with this technology, no such irritation was observed in the earlier clinical trials using similar formulations," Kumar says.
The cost of spray-on administration has not been determined, but nestorone is not expensive and the system can be refilled with canisters, so the cost of the system is a one-time cost with additional costs only when the canister is changed each month, Kumar and Sitruk-Ware say.
A spray-on birth control method provides yet another possible solution to the world’s need for different contraceptive options for women and couples in developed and developing countries, they add.
"The greater the number of options, the higher the probability that users will find a convenient method that suits their needs and will be compliant with it," Sitruk-Ware says.
While it’s too early to run acceptability studies for the contraceptive spray, a large acceptability study in several countries is warranted, she notes.
The advantage of this mode of delivery is related to the nonoral administration of steroids and also to the fact that it is not visible as a patch, Sitruk-Ware adds.
"As compared to the gel, it is not sticky and dries very quickly," she says. "Studies conducted previously with Nestorone gel in Latin America were very successful, and women liked this method."3,4,5
1. Sitruk-Ware R, Small M, Kumar N, et al. Nestorone: Clinical applications for contraception and HRT. Steroids 2003; 68:907-913.
2. Johansson ED, Sitruk-Ware R. New delivery systems in contraception: Vaginal rings. Am J Obstet Gynecol 2004; 190(4 Suppl):S54-9.
3. Jordan A. Toxicology of progestogens of implantable contraceptives for women. Contraception 2002; 65:3-8.
4. Massai MR, Diaz S, Quinteros E, et al. Contraceptive efficacy and clinical performance of Nestorone implants in postpartum women. Contraception 2001; 64:369-376.
5. Harwood B, Mishell DR. Contraceptive vaginal rings. Semin Reprod Med 2001; 19:381-390.