Scientists eye delivery options in microbicides
The last patient on your list is a young woman with a positive test for a sexually transmitted disease (STD). When discussing strategies for protection from future infections, she tells you she is not comfortable with using a female condom and has problems negotiating male condom use with her boyfriend. Outside of abstinence, what are her options?
Scientists now are looking at microbicides — substances designed, when applied vaginally, to reduce transmission of HIV or other STDs — to give women more protection options. Ten candidates are in Phase I or I/II studies, six in Phase II/IIb, and four in Phase III trials.1 According to Contraceptive Technology, look to at least 2007 before a candidate will be ready for FDA approval.2
Microbicide formulations are being analyzed in several delivery methods, including gels, creams, films, suppositories, and vaginal rings. One microbicidal candidate, TMC120, is being evaluated for use in a vaginal ring as well as in a topical gel, says Mark Mitchnick, MD, chief scientist at International Partnership for Microbicides (IPM) in Silver Spring, MD, a nonprofit organization.
The microbicide, a non-nucleoside reverse transcriptase inhibitor, is in advanced safety trials in Africa, he reports. If results from the safety trial are positive, scientists look toward implementing a Phase III efficacy trial in 2007, Mitchnick estimates.
IPM completed a small safety trial of TMC 120 gel in vaginal ring form last July. Thirteen women participated in the Ghent, Belgium, study, using the ring for seven consecutive days. Warner Chilcott PLC, based in Northern Ireland, developed the ring, and IPM collaborated with Medisearch International and the University of Ghent, both based in Belgium, to conduct the study, which is not yet published. Results from an earlier trial indicate that rings are capable of releasing amounts needed to prevent infection.3
Ring applicators would offer women the convenience of fewer applications; however, the delivery method offers some restrictions, notes Mitchnick. It is more difficult to combine compounds to work effectively in ring delivery, he observes. There are a limited number of ring manufacturers. Production of rings would need to be stepped up if scientists can show that a microbicidal candidate is safe and effective in such a delivery mechanism, Mitchnick states.
Barrier method in focus
Amphora, an acid-buffering bioadhesive vaginal formulation also known as Acidform, is in research in Madagascar to test its acceptance by urban women at high risk for STDs. The study is cosponsored by the Centers for Disease Control and Prevention (CDC) in Atlanta, the United States Agency for International Development in Washington, DC, the Contraceptive Research and Development (CONRAD) program in Arlington, VA, and the University of North Carolina at Chapel Hill.
Amphora is being tested in Madagascar with the diaphragm as a cervical barrier device. Previous research indicates that acceptance of such a barrier device is high among the women in the study population.4 Studies indicate that Amphora is safe and well tolerated by men and women.5,6
What are some potential advantages of using a barrier device to deliver a microbicide? "Any kind of barrier device can slow or inhibit movement of pathogens to the cervix, and more importantly, will hold a microbicide in the vagina by preventing it from leaking out," explains Barbara North, MD, medical director of Instead, the San Diego manufacturer of Amphora. "Also, since barrier devices have two sides, you can technically use both the inside and the outside to deliver appropriate substances to either the vaginal or the cervical tissue."
Instead also is looking at use of Amphora as a possible contraceptive in combination with its Instead Softcup, says Ariel Herr, company spokesperson. The Softcup is marketed as a feminine hygiene product. While Amphora received Food and Drug Administration (FDA) approval in September 2004 as a personal lubricant, the company has not yet released it on the retail market, says Herr.
"Instead is currently in discussions with various public funded organizations and research groups to discuss the scope and timing of a trial for the company’s proposed Choice Cup contraceptive device, which will combine the company’s flagship Instead Softcup as a disposable diaphragm with its candidate microbicide Amphora as a spermicide," says Herr. "While Amphora will be monitored for contraceptive effectiveness in the 2006 CDC clinical trial that will follow the current pre-clinical in Madagascar, the company also aims to launch a Choice Cup trial in 2006 to eventually make the product available to and accessible for women around the world."
- Alliance for Microbicide Development. Microbicide Clinical Trials Summary Table. Accessed at www.microbicide.org/publications/digest/Microbicide.Clinical.Trials.Summary.Table.December.2005.pdf.
- Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology: 18th revised edition. New York City: Ardent Media; 2004.
- Malcolm RK, Woolfson AD, Toner CF, et al. Long-term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings. J Antimicrob Chemother 2005; 56:954-956.
- Behets F, Turner AN, Van Damme K, et al. Acceptability and feasibility of continuous diaphragm use among sex workers in Madagascar. Sex Transm Infect 2005; 81:472-476.
- Amaral E, Faundes A, Zaneveld L, et al. Study of the vaginal tolerance to Acidform, an acid-buffering, bioadhesive gel. Contraception 1999; 60:361-366.
- Schwartz JL, Poindexter A, Schmitz SW, et al. Male tolerance of ACIDFORM gel. Contraception 2005; 71:443-446.