Potential spermicide enters advanced trial

Scientists are evaluating an experimental vaginal gel for use as a potential spermicide in a Phase III clinical trial.

Amphora, under development by Evofem of San Diego, is a bioadhesive acid-buffering gel that coats the vaginal wall and cervix. Amphora helps maintain a woman's natural pH level between 3.8 and 4.2. Earlier research findings indicate this level renders sperm immobile and inactivates most sexually transmitted infectious organisms, including gonococci, herpes, chlamydia, HPV, and HIV.1-4

Investigators are enrolling women in 32 U.S. clinical sites, says Krystle Ficco, a Evofem spokesperson. The multicenter, open-label, randomized, controlled trial will examine use of Amphora gel compared to Ortho Options Conceptrol vaginal gel over seven cycles of use. The study design will allow women using Amphora to continue with study treatment for up to 13 cycles of treatment upon completion of the first seven cycles.

While spermicides do not offer the highest level of contraceptive effectiveness, they do represent an easily accessible, reversible form of birth control that is female-controlled. Among typical couples who initiate use of vaginal spermicides, about 29% will experience an accidental pregnancy in the first year. If vaginal spermicides are used consistently and correctly, about 18% will become pregnant.5

How does it work?

Amphora works by two primary mechanisms of action. As a vaginal pH buffer, it enhances the vagina's natural defenses by maintaining normal acidic pH during the introduction of semen (an alkaline substance) during intercourse. As a bioadhesive barrier, the chemical agent forms a protective physical barrier over the cervix and vaginal walls. Sperm and microbes are unable to penetrate the vaginal wall and cervix due to Amphora's ability to create a protective, long-lasting coating over the vaginal surface.

Originally developed by the Topical Prevention of Conception and Disease (TOPCAD) Program at Rush–Presbyterian–St. Luke's Medical Center, Chicago, Amphora was licensed to Evofem's former company, Instead, in 2002, with patent protection granted in March 2004. Shortly thereafter, Amphora was granted clearance for use as a personal lubricant by the Food and Drug Administration (FDA). However, it has not yet been marketed as such, says Ficco.

"The approval was a critical milestone in the ongoing evolution of this product, giving us opportunities to work with the FDA and opening up more doors for clinical study," Ficco states.

Alternative to N-9?

Scientists are looking for alternatives to nonoxynol-9 (N-9), which is the chemical basis of current spermicides in the United States. Research has shown that frequent use of N-9 can cause genital lesions in the vagina and might increase the risk of HIV transmission.6 It also has been found to cause damage to the lining of the rectum, providing an entry point for HIV and other sexually transmitted infections (STIs).7

According to Centers for Disease Control and Prevention guidelines, spermicides—especially those that contain N-9—should not be used for STI prevention. Furthermore, N-9 lubricants should not be used during anal intercourse.7

The impetus for Amphora is to provide a less-irritating spermicide, with its attendant benefits; preliminary results indicate that it might be a good microbicide as well, says Michael Rosenberg, MD, MPH, clinical professor of obstetrics and gynecology in the School of Medicine at the University of North Carolina, Chapel Hill.

Rosenberg serves as chief executive officer of Health Decisions, a Chapel Hill, NC research firm that is participating in the Amphora clinical trial.

"I'm always impressed that I've been working on microbicides for more than 15 years, and still all we have is N-9," says Rosenberg. "I don't think N-9 is bad, but I would hope there is something better."

References

  1. Garg S, Anderson RA, Chany CJ 2nd, et al. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 2001; 64:67-75.
  2. Spencer SE, Valentin-Bon IE, Whaley K, et al. Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model. J Infect Dis 2004; 189:410-419.
  3. Tuyama AC, Cheshenko N, Carlucci MJ, et al. ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: optimal candidate for microbicide combinations. J Infect Dis 2006; 194:795-803.
  4. Herold BC, Kirkpatrick R, Marcellino D, et al. Bile salts: natural detergents for the prevention of sexually transmitted diseases. Antimicrob Agents Chemother 1999; 43:745-751.
  5. Hatcher RA, Trussell J, Nelson, AL, et al. Contraceptive Technology. 19th ed. New York, NY: Ardent Media; 2007.
  6. Wilkinson D, Tholandi M, Ramjee G, et al. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomized controlled trials including more than 5,000 women. Lancet Infect Dis 2002; 2:613–617.
  7. Centers for Disease Control and Prevention. New CDC treatment guidelines critical to preventing health consequences of sexually transmitted diseases. Fact sheet. Accessed at http://www.cdc.gov/media/pressrel/fs020509.htm.