td-4208 and Renal-Insufficiency

Revefenacin, a long-acting muscarinic antagonist for nebulization, has been shown to improve lung function in patients with chronic obstructive pulmonary disease. Here we report pharmacokinetic (PK) and safety results from two multicenter, open-label, single-dose trials evaluating revefenacin in subjects with severe renal impairment (NCT02578082) and moderate hepatic impairment (NCT02581592).. The renal impairment trial enrolled subjects with normal renal function and severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m. In the renal impairment study, the maximum observed plasma revefenacin concentration (C. Systemic exposure to revefenacin increased modestly in subjects with severe renal impairment but was similar between subjects with moderate hepatic impairment and normal hepatic function. The increase in plasma exposure to THRX-195518 in subjects with severe renal or moderate hepatic impairment is unlikely to be of clinical consequence given its low antimuscarinic potency, low systemic levels after inhaled revefenacin administration, and favorable safety profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzamides; Carbamates; Female; Hepatic Insufficiency; Humans; Male; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Renal Insufficiency; Severity of Illness Index; Young Adult