title: In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials.
abstract: The development of vaginal microbicides for the prevention of sexual transmission of HIV is becoming an increasingly important strategy in the battle against the AIDS epidemic. Several first generation microbicide candidates are entering Phase III efficacy trials, and several other candidates are in earlier stages of clinical development. The capacity to make accurate clinical assessments of the safety and efficacy of microbicide formulations is critical. Since microbicide trials will rely on a blinded, randomized, placebo-controlled design, it is important to employ a placebo formulation that does not distort either safety or efficacy assessments. Efficacy of the microbicide would be underestimated if the placebo itself provided a degree of protection. Conversely, a placebo with epithelial toxicity that increased susceptibility would cause an overestimation of microbicide efficacy. To address these issues, a hydroxyethylcellulose (HEC) placebo formulation has been developed and has been adopted for use in clinical evaluations of investigational microbicides as a "universal" placebo. In this report, the chemical and physical properties of this formulation are described, as well as its in vitro and in vivo effects on safety and efficacy. The results show that this "universal" placebo has adequate physical properties, is sufficiently stable as a vaginal gel formulation, and is safe and sufficiently inactive for use in the clinical study of investigational microbicides.
authors.affiliation: Biosyn, Inc., Huntingdon Valley, PA 19006, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Tien
authors.forename: Roger L
authors.initials: RL
authors.lastname: Schnaare
authors.forename: Feirong
authors.initials: F
authors.lastname: Kang
authors.forename: Gina
authors.initials: G
authors.lastname: Cohl
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McCormick
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Moench
authors.forename: Gustavo
authors.initials: G
authors.lastname: Doncel
authors.forename: Karen
authors.initials: K
authors.lastname: Watson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Jill
authors.initials: J
authors.lastname: Schwartz
authors.forename: Karen
authors.initials: K
authors.lastname: Douville
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Romano
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008251:Macaca; D010919:Placebos; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic; D014621:Vagina; D014783:Viscosity
chemical_list: D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D010919:Placebos