Spray-on contraceptive moves to next step

Scientists are preparing to take the next step in the search for a spray-on contraceptive, with a Phase II trial scheduled for the second half of 2006.

Acrux, a pharmaceutical company based in Melbourne, Australia, has entered into an agreement with the Population Council, a New York City-based research group, to develop a contraceptive spray containing the council’s synthetic progestin, Nestorone. The upcoming Phase II trial will evaluate whether the spray inhibits ovulation, states Diane Rubino, Population Council spokeswoman.

Acrux and the Population Council began working together in 2003, using Acrux’s Metered Dose Transdermal System (MDTS) technology to deliver Nestorone to the skin. MDTS is a hand-held aerosol drug delivery system. The contraceptive spray, delivered via MDTS, would be painless, easy to use, and convenient, the developing organizations say.

According to Igor Gonda, chief executive officer of Acrux, market research has shown that many women will prefer the ease and convenience of this method to swallowing pills, taking injections, or wearing patches.

"The target feature of Nestorone MDTS is a convenient daily spray onto the arm that is more discreet and less irritating to the skin than a patch, and, we believe, will prove to have a better safety profile than other hormonal contraceptives," states Gonda.

Results of the Phase I, proof-of-concept, pharmacokinetic study were presented at the Washington, DC-based Biotechnology Industry Organization’s 2005 Annual International Convention. The study was conducted in six healthy women at the Sydney Centre for Reproductive Health Research in New South Wales, Australia. Findings indicate that once-a-day dosing of the Nestorone Metered Dose Transdermal System contraceptive spray provided sustained delivery of the contraceptive agent. Mean serum concentrations of Nestorone were maintained in the target range expected to be effective for contraception. The spray was well tolerated, with no serious adverse events recorded.1

Nestorone falls into the category of 19-nor derivatives of progesterone, which are referred to as "pure" progestational molecules, as they bind almost exclusively to the progesterone receptor without interfering with receptors of other steroids.1 Nestorone has strong progestational activity and antiovulatory potency, with no androgenic or estrogenic activity in vivo.1

The synthetic progestin is being considered for use in several potential contraceptive formulations, including vaginal rings, implants, and transdermal systems.2

Scientists performed a multicenter one-year dose-finding trial of contraceptive vaginal rings that utilized Nestorone, evaulating three dose combinations of Nestorone and ethinyl estradiol with respect to 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.3

Researchers also are examining the use of a Nestorone ring in emergency contraception. Investigators conducted a Phase I clinical trial of a ring with a 15 mcg ethinyl estradiol/150 mcg Nestorone formulation; results suggest the ring may be used as an emergency contraceptive method.4

The Metered Dose Transdermal System involves drug delivery via a spray applied once a day. The patient simply pushes a metering pump, similar to those used for nasal sprays, and sprays the formulation on the skin via a proprietary applicator. The spray most likely would be applied to the skin of the woman’s forearm. The alcoholic component of the formulation, which is a solution of the drug and the enhancer in alcohol, rapidly evaporates, and the drug and enhancer permeate the skin and form a drug reservoir in the skin.

Acrux is evaluating its MDTS technology in other products. It has licensed U.S. rights for two formulations to VIVUS of Mountainview, CA. One prospective formulation, Evamist, is in Phase III development for treatment of menopausal symptoms. Another investigational formulation, testosterone MDTS, is being evaluated for treatment of decreased libido in women. Phase II development has been completed for that formulation, according to the company.

References

  1. Acrux and Population Council. Clinical trial of the world’s first contraceptive spray for women: Acrux and Population Council announce positive data. Press release. June 20, 2005.
  2. Sitruk-Ware R, Small M, Kumar N, et al. Nestorone: Clinical applications for contraception and HRT. Steroids 2003; 68:907-913.
  3. 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.
  4. Croxatto HB, Brache V, Massai R, et al. Feasibility study of Nestorone-ethinyl estradiol vaginal contraceptive ring for emergency contraception. Contraception 2006; 73:46-52.