Common warts, those found on the hands, tops of the feet, and sometimes on the face, arms and legs, may persist for years and may increase in size and number. Some warts may convert to cancers, and the wart virus, human papillomavirus, is the cause of cervical cancer accounting for more than 250,000 deaths annually of women worldwide. The objectives of this proposal are to develop marketable, topical formulations of tetraethylammonium chloride (TEAC) for the treatment of human papillomavirus-induced common warts. This work is directly related to the current support of FDA regulatory submissions for this indication. The proposal describes the manufacturing process, pharmacology, and toxicology studies (to establish safety and antiviral activity of the formulations), required to proceed forward with the series of FDA Phase l/ll clinical trials needed to establish therapeutic efficacy and safety in man. The initial formulation identification, optimization, and selection procedures (that include evaluation of the antiviral activity of promising formulations), were accomplished in the Phase I SBIR grant. This Phase II proposal includes: 1) Development of analytical methods for monitoring TEAC and its degradants; 2) Manufacture of formulations under Good Manufacturing Procedures for use in toxicology and clinical studies, as well as formulation stability studies; 3) Evaluation of the safety of TEAC formulations in animal models for primary skin and eye irritation; 4) Evaluation of TEAC formulation toxicity in a topical repeat-dose study in minipigs; 5) Clinical demonstration in a 21-day cumulative irritation study that the lead TEAC formulation is a non-irritant; and 6) Clinical demonstration of safety and efficacy of the lead TEAC formulation in a proof-of principle study in patients with common warts. TEAC, a compound with known antiviral activity, has a very promising safety profile in humans and affords a significant opportunity to become the first FDA-approved topical product for the treatment of common warts. ? ?
