Fotivda: which tox species, and why?

“The selection of animal models to be used in toxicology and safety pharmacology studies (rats and monkeys) was based on PK and/or metabolic profiles of tivozanib.”

“Comparison of the metabolic profile of tivozanib in liver microsomes showed that monkey most closely resembled the human, followed by the rat. These data provided support for species selection.”

“Oral administration of tivozanib in rats for 26 weeks produced non-adverse decreases in body weights, abnormal whitening of the teeth and changes in hematology/clinical chemistry at 0.08 mg/kg/day.”

“Single-oral and intravenous (IV) dose toxicity studies in CD-1 mice and Sprague-Dawley (SD) rats were conducted followed by oral repeat-dose studies in SD rats (up to 26 weeks) and cynomolgus monkeys (up to 39 weeks).”

“Tivozanib was shown to be teratogenic, embryotoxic and foetotoxic in pregnant rats at dose levels 5 times lower than the recommended clinical dose (based on a 60 kg human). Studies in pregnant rabbits showed no effect on maternal health or embryo foetal development at doses approximately 0.6 times the human exposure at the recommended dose”

“Carcinogenicity studies have not been conducted with tivozanib.”

“The selection of animal models to be used in toxicology and safety pharmacology studies (rats and monkeys) was based on PK and/or metabolic profiles of tivozanib.”