Cobenfy: which tox species, and why?

“The binding affinity and functional activity of xanomeline at the mAChR receptors were generally similar between human and animal species (rat and monkey), therefore, supporting the use of the rat and monkey as the nonclinical species for pharmacology and toxicology evaluation.”

“The binding affinity and functional activity of xanomeline at the mAChR receptors were generally similar between human and animal species (rat and monkey), therefore, supporting the use of the rat and monkey as the nonclinical species for pharmacology and toxicology evaluation.”

“In addition, the Applicant conducted toxicity studies with the combination via oral gavage, including repeat-dose toxicity studies in the rat for up to 90 days; embryofetal development toxicity studies in the rat and rabbit; and pre- and postnatal toxicity study with an additional follow-up pre- and postnatal study with xanomeline alone in the rat.”

“The nonclinical studies for the NDA included toxicity studies conducted with xanomeline alone via dietary administration in the rat and mouse, nasogastric intubation in the monkey, and subcutaneous injection in the rat and monkey.”

“In addition, the Applicant conducted toxicity studies with the xanomeline/trospium combination via oral gavage, including repeat-dose toxicity studies in the rat for up to 90 days, embryofetal development studies in the rat and rabbit, and pre- and postnatal development studies in the rat.”

“Nonetheless, in the rat and mouse carcinogenicity studies, oral administration of xanomeline via the diet did not cause necrotic lesions or progress into neoplastic tumors in the liver at doses up to 1.5 and 3 times the MRHD (125 mg BID) of xanomeline.”

“The binding affinity and functional activity of xanomeline at the mAChR receptors were generally similar between human and animal species (rat and monkey), therefore, supporting the use of the rat and monkey as the nonclinical species for pharmacology and toxicology evaluation.”