Duvyzat: which tox species, and why?

“The toxicity of givinostat was investigated after single and repeated i.v. and oral administration for up to 13 weeks in mice, 26 weeks in rats 4 weeks in dogs and 39 weeks in monkeys.”

“Mice and rats were chosen as pharmacologically responsive rodent species, whereas monkeys were selected due to the limited gastrointestinal tolerability of givinostat in the 4 weeks repeat-dose toxicity study in dogs.”

“The toxicity of orally administered givinostat was investigated in single and repeat-dose studies for up to 13 weeks in mice, 26 weeks in rats 4 weeks in dogs and 39 weeks in monkeys.”

“The toxicity of givinostat was investigated after single and repeated i.v. and oral administration for up to 13 weeks in mice, 26 weeks in rats 4 weeks in dogs and 39 weeks in monkeys.”

“These investigations are complemented by genotoxicity evaluations, reproductive and developmental toxicity studies in rats and rabbits including also juvenile animals.”

“PMR 4575-1 Conduct a carcinogenicity study of givinostat in mouse. • Final Protocol Submission: 12/2022 (submitted) • Study Completion: 12/2024 • Final Report Submission: 12/2025 PMR 4575-2 Conduct a 2-year carcinogenicity study of givinostat in rat.”

“In both models, daily oral administration of givinostat delayed decreases in treadmill exhaustion, grip strength, and muscle fibrosis and adipocyte infiltration.”