2 trials will examine capability of microbicide

Can a new microbicide offer effective protection against pregnancy? How does it perform when it comes to prevention of HIV? Two trials of a polymeric gel are in the works to shed further light on these reproductive health questions.

BufferGel is a spermicidal and microbicidal gel formulated to maintain the natural protective acidity of the vagina. Investigators at 10 U.S. sites began enrolling women in October 2001 for a contraceptive efficacy trial of the gel formulation, reports Richard Cone, PhD, professor of biophysics at Johns Hopkins University and managing director of ReProtect LLC, both in Baltimore. The polymeric gel was developed jointly by researchers at the university and the private firm.

The microbicide will be the focus of another trial this summer to determine its efficacy in preventing HIV transmission, says Thomas Moench, MD, medical director for ReProtect LLC. The trial, a multicenter investigation in Africa and Asia, will look at BufferGel and another microbicide, PRO 2000 from Interneuron of Lexington, MA. The investigation is part of the HIV Prevention Trials Network coordinated by the Bethesda, MD-based National Institutes of Health. (Contraceptive Technology Update reported on BufferGel, PRO 2000, and other microbicides in an April 1999 article, p. 37, "Get Ready: Women to Have More Options for Preventing Disease.")

Birth control option?

The contraceptive study is designed to test whether women using BufferGel and a diaphragm can reduce the risk of pregnancy as effectively as women using a conventional spermicidal detergent and a diaphragm. Investigators plan to enroll 1,000 women, who must be in a sexually active and monogamous relationship and at low risk for infection by sexually transmitted diseases. They must agree not to use other forms of contraception beyond that supplied by the study and be willing to risk getting pregnant.

The clinical sites are Eastern Virginia Medical School in Norfolk; Women’s Health Institute in New Brunswick, NJ; University of Pennsylvania Medical Center in Philadelphia; Magee-Womens Hospital in Pittsburgh; University of Florida in Jacksonville; California Family Health Council in Los Angeles; University of Colorado Health Sciences Center in Aurora; University of Cincinnati; New York University and the College of Physicians and Surgeons of Columbia University, both in New York City.

Early research found the formulation effective in animal models,1 and standard postcoital testing determined BufferGel to have in vivo spermicidal action.2 The research under way will further examine the polymeric gel’s contraceptive effectiveness in a clinical trial.

Check safety profile

Two small studies have been published on the safety of BufferGel. One investigation was focused in the United States;3 the other was conducted at four international sites: Pune, India; Chiang-Mai, Thailand; Blantyre, Malawi; and Harare, Zimbabwe.4

In the U.S. study, 27 participants initially used the product once daily for 14 days and then twice daily for 14 days. They underwent colposcopy before and after product exposure. The formulation was well tolerated, although two-thirds of the participants reported at least one mild or moderate adverse experience. The most common adverse events were irritative genitourinary symptoms, according to the study. The majority of the study participants said they would use the product if it were commercially available.

In the international study, BufferGel was evaluated by 98 women for vaginal use twice daily. The formulation was found to be safe and well tolerated by the cervicovaginal epithelium. Irritation was generally mild and of short duration, study results indicate.

No detergent activity

BufferGel is applied vaginally before intercourse, like conventional spermicides; however, it does not use detergent activity to inactivate sperm. It simply reinforces the mild acidity that occurs naturally in the vagina, says Cone. Developers wanted to avoid detergent activity since it can irritate the vaginal lining after frequent use.

The formulation must be able to provide "sperm and germ" protection, as well as maintain the vaginal flora, all in an acceptable product that women will use, notes Cone. BufferGel has met those standards in animal trials and in extensive clinical safety trials, he believes.

References

1. Zeitlin L, Hoen TE, Achilles SL, et al. Tests of BufferGel for contraception and prevention of sexually transmitted diseases in animal models. Sex Transm Dis 2001; 28:417-423.

2. Moench T, Baker J, Cone R, et al. BufferGel is an active spermicide in the standard postcoital test. Presented at the Microbicides 2000 conference. Washington, DC; March, 2000.

3. Mayer KH, Peipert J, Fleming T, et al. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis 2001; 32:476-482.

4. Van De Wijgert J, Fullem A, Kelly C, et al. Phase 1 trial of the topical microbicide BufferGel: Safety results from four international sites. J Acquir Immune Defic Syndr 2001; 26:21-27.