PROJECT
Clinical Studies: Carraguard® and Other Phase 1 Safety Trials  

Phase 1 Safety Trials of Carrageenan-based Candidate Microbicidal Gels
Once laboratory research has shown that human testing of a promising product is appropriate, a Phase 1 safety trial (with a small number of healthy volunteers) is conducted to ensure that the product does not cause harm in people.

The Population Council has conducted a number of Phase 1 safety trials of vaginal use of carrageenan-based candidate microbicidal gels in healthy HIV-negative women. In 1996, the US Food and Drug Administration (FDA) gave the Council an Investigational New Drug (IND) approval for an iota-carrageenan-based microbicidal gel (PC-213). The gel was tested in a Phase 1 trial with 25 sexually abstinent women in Australia, Chile, the Dominican Republic, Finland, and the United States. The women inserted the gel once a day for seven days. Results showed that none of the women experienced any significant irritation of the reproductive tract.

Research concurrent with the Phase 1 trial of PC-213 showed that lambda-carrageenan was more promising as a potential microbicide than iota-carrageenan. Therefore the Population Council obtained another IND approval from the FDA in the fall of 1997 for lambda-carrageenan (PC-503). This gel was then tested in a Phase 1 trial with 35 sexually abstinent women in Australia, Chile, the Dominican Republic, Thailand, and the United States. These women also inserted the gel once a day for seven days. None of the women in this study experienced any significant irritation of the reproductive tract.

Additional Phase 1 Safety Trials of the Candidate Microbicidal Gel Carraguard
Study among HIV-negative couples. In June 2001, the Population Council and the Thai Ministry of Public Health–CDC Collaboration began an expanded safety trial of Carraguard among 55 HIV-negative couples in Chiang Rai, who used Carraguard or its matching placebo for six months. The trial protocol was similar to that of the expanded safety and acceptability (Phase 2) trials. However, for the first time men also were examined for safety (the effect of study gel on the penile skin) and interviewed about compliance and acceptability. Data collection was completed in 2002; results indicated that Carraguard was both safe and acceptable for men.

Study among HIV-positive individuals. Many of the communities where a microbicide is likely to be widely used have high rates of HIV infection. Further, many of the women and couples who decide to use a microbicide will be unaware that they are HIV-infected. Women who know that they are HIV-positive may still wish to use a microbicide to avoid infection with other sexually transmitted pathogens or to protect their partners from infection. For these reasons, it is important to know whether people who are HIV-positive can safely use a potential microbicide.

The Population Council conducted a Phase 1 safety trial of Carraguard in HIV-positive women and men in Durban, South Africa, in collaboration with the South African Medical Research Council. The product was found to be safe and acceptable to sexually abstinent men and women as well as sexually active women.

Another Phase 1 safety trial of Carraguard in HIV-positive women was conducted in Chiang Rai, Thailand, in collaboration with the Thailand Ministry of Public Health–CDC Collaboration. The trial included 60 women who used Carraguard gel, matching placebo gel, and no gel, in a cross-over study design. Carraguard and the placebo gels were found to be safe and they also did not increase genital shedding. Both study gels were acceptable to women, although Carraguard was preferred when women were asked to compare their experiences with the two gels.

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Related Projects

• Clinical Studies: Carraguard® Phase 2 Expanded Safety and Acceptability Trials

• Clinical Studies: Carraguard® Phase 3 Efficacy Trial

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