Vanrafia: how was the first human dose set?

“Initially, the study was designed as a single dose, dose-escalating study with the starting dose of 139.5 mg.”

“In the chronic toxicology studies of atrasentan in the rat and dog, a no-observed-adverse-effect level (NOAEL) was not established. In male rats, the lowest dose tested, i.e., 5 mg/kg/day, was considered to be the lowest-observed-adverse-effect level (LOAEL) because of modest testicular degeneration”