Cardamyst: which tox species, and why?

“General toxicity studies were conducted with intranasal administration of etripamil for durations of up to 14 days in rats (once daily [QD]) and 6 months (once weekly) in monkeys.”

“Rats (rodent) and monkeys (nonrodent) were selected as appropriate animal species for toxicity testing because etripamil is rapidly metabolized to a primary inactive metabolite (MSP-2030) similarly in rats, monkeys, and humans.”

“No mortality, body weight changes, clinical chemistry, organ weights, macroscopic, or systemic microscopic findings were associated with the administration of etripamil up to 5.7 mg/kg/week.”

“General toxicity studies were conducted with intranasal administration of etripamil for durations of up to 14 days in rats (once daily [QD]) and 6 months (once weekly) in monkeys.”

“The Applicant has conducted all the pivotal reproductive toxicity studies (embryo-fetal development in rats and rabbits, fertility and early embryonic development, and pre- and postnatal development in rats) via intravenous route of administration QD, as opposed to the intranasal route to achieve adequate exposures during critical organogenesis period.”

“No carcinogenicity studies were conducted.”

“Rats (rodent) and monkeys (nonrodent) were selected as appropriate animal species for toxicity testing because etripamil is rapidly metabolized to a primary inactive metabolite (MSP-2030) similarly in rats, monkeys, and humans.”