Thrombin and thrombin peptides play a role in initiating tissue repair. The potential safety and efficacy of TP508 (Chrysalin®) treatment of diabetic foot ulcers was evaluated in a 60-subject, prospective, randomized, double-blind, placebo-controlled phase I/II clinical trial. Chrysalin® in saline or saline alone was applied topically, twice weekly, to diabetic ulcers with standardized care and offloading. A dose-dependent effect was seen in the per-protocol population where 1 and 10 μg Chrysalin® treatment resulted in 45 and 72% more subjects with complete healing than placebo treatment. Chrysalin® treatment of foot ulcers more than doubled the incidence of complete healing ( p<0.05), increased mean closure rate ∼80% ( p<0.05), and decreased the median time to 100% closure by ∼40% ( p<0.05). Chrysalin® treatment of heel ulcers within this population resulted in mean closure rates 165% higher than placebos ( p<0.02) and complete healing in 86% (6/7) of ulcers compared with 0% (0/5) of placebo ulcers ( p<0.03). Local wound reactions and adverse events (AEs) were equal between groups with no reported drug-related changes in laboratory tests or serious AEs. These results indicate the potential safety and efficacy of Chrysalin® for treatment of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]