Zurzuvae: which tox species, and why?

“The toxicologic and toxicokinetic (TK) profile of orally administered zuranolone was assessed in a series of single and repeat dose studies in rats and dogs for up to 6 and 9 months, respectively.”

“All human metabolites detected at greater than 1% of drug, were also detected in rat or dog plasma.”

“In the pivotal 9-month study in dogs (0, 0.6, 1.2 and 2.5 mg/kg), sedation, sedation-related clinical signs (impaired equilibrium, hypoactivity, ataxia, tremors, and being prostrate) and increased heart rate and mortality were observed.”

“The toxicologic and toxicokinetic (TK) profile of orally administered zuranolone was assessed in a series of single and repeat dose studies in rats and dogs for up to 6 and 9 months, respectively.”

“Embryo-foetal development GLP studies were conducted in pregnant Sprague Dawley rats Crl:CD1(ICR) mice and rabbits.”

“The carcinogenic potential of zuranolone was tested in a 6-month Tg.rasH2 transgenic mouse assay and in a 2-year rat carcinogenicity study. Both studies were adequately conducted and, according to the Food and Drug Administration (FDA) statistical analyses, negative for drug-induced tumors.”

“In the pivotal 9-month study in dogs (0, 0.6, 1.2 and 2.5 mg/kg), sedation, sedation-related clinical signs (impaired equilibrium, hypoactivity, ataxia, tremors, and being prostrate) and increased heart rate and mortality were observed.”