Abstract 5462: Single dose dermal irritation study of apaziquone in rabbits

Abstract

Abstract Introduction and Objectives: Apaziquone is a novel bioreductive alkylating agent in development for intravesical therapy of nonmuscle invasive bladder cancer (NMIBC). The standard dose of apaziquone in all ongoing clinical studies is 4 mg/ 40 mL (0.1mg/mL). For clinical use, lyophilized apaziquone is reconstituted with diluent and instilled in the bladder. During the preparation and handling of the product, there is a possibility of accidental dermal contact for the healthcare professionals. To date, dermal irritation potential of apaziquone has not been investigated. The purpose of this study was to evaluate the dermal irritation potential of apaziquone in rabbits. Materials & Methods: Apaziquone was administered topically on the skin (non-occlusive) to New Zealand White (NZW) rabbits as a single dose for 4 hours followed by removal of excess material, and skin examination for up to 72 hours after removal of excess material. Each male NZW rabbits (3/group; one group) had three identified treatment sites on the back: (1) untreated (2) vehicle (diluent for apaziquone) and (3) apaziquone (0.1 mg/mL). Animals were treated with a single non-occlusive dermal dose of apaziquone (0.5 mL of 0.1 mg/mL) and vehicle for 4 hours followed by removal of excess material. No test material or vehicle was applied to the site designated as untreated. The treatment sites were observed and scored at baseline and at various times (4, 24, 48, and 72 hours) after removal of excess test article and vehicle. The following parameters were evaluated: viability, clinical observations, and dermal observations/scoring by modified Draize method. Results: No clinical signs of toxicity were observed during the study and no signs of dermal irritation related to test article or vehicle/diluent were observed at any of the dose sites in any of animals. The Primary Dermal Irritation Index for apaziquone, administered at clinically relevant exposures, had a value of zero (0) indicating no irritation at the concentration and for the duration of exposure. Conclusion: Apaziquone did not cause any dermal irritation in rabbits at a clinically relevant concentration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5462. doi:1538-7445.AM2012-5462