Isturisa: which tox species, and why?

“In repeated-dose toxicity studies osilodrostat was tested in mice for up to 13 weeks at 10 to 200 mg/kg/day, in rats for up to 26 weeks at 0.2 to 50 mg/kg/day and in dogs for up to 39 weeks at 0.1 to 10 mg/kg/day.”

“Pharmacokinetic and metabolic profiles were qualitatively similar between humans and nonclinical species used for evaluating the potential toxicity or osilodrostat thereby supporting the translatability of the findings from these studies.”

“39-Week Oral Gavage Chronic Toxicity and Toxicokinetic Study with LCI699 in Dogs with a 4-Week Recovery Period”

“The NOAELs observed in the 26- and 39-week repeated-dose toxicity studies in the rat and the dog were 2.0 and 10 mg/kg/day, respectively, based on the frequency and severity of findings in the liver and female reproductive”

“Effects on fertility were evaluated in the rat and embryofetal development was assessed in the rat and rabbit.”

“Carcinogenicity studies were conducted in Wistar Han rats and CD1 mice.”

“The toxicity of osilodrostat was assessed in a series of repeat-dose toxicity studies that were conducted in mice, rats, and dogs, including chronic (rat and dog) and carcinogenicity (mouse and rat) studies.”