LAUSR

Sparsentan is a single‐molecule dual antagonist of the endothelin type A receptor and angiotensin II type 1 receptor under investigation for the treatment of focal segmental glomerulosclerosis and immunoglobulin A nephropathy. Dapagliflozin, a sodium‐glucose cotransporter 2 inhibitor, has recently been indicated in chronic kidney disease. Sparsentan may be considered for concomitant use with dapagliflozin. The purpose of this open‐label, 1‐sequence crossover study was to determine whether drug–drug interactions between sparsentan and dapagliflozin affect dapagliflozin pharmacokinetics (PK). In addition, exposure to the inactive metabolite of dapagliflozin, dapagliflozin‐3‐O‐glucuronide, was used to evaluate the effect of sparsentan on the primary metabolizing enzyme of dapagliflozin, uridine 5′‐diphospho‐glucuronosyltransferase 1A9. The study included 22 healthy adults treated with 10 mg of dapagliflozin on day 1, and 800 mg/day of sparsentan on days 5–14, with a 10‐mg dose of dapagliflozin coadministered on day 11. PK samples were taken for dapagliflozin, dapagliflozin‐3‐O‐glucuronide, and sparsentan before and after treatment throughout the study. Steady‐state concentrations of sparsentan following daily dosing did not affect the PK of single‐dose dapagliflozin in healthy adults. Dapagliflozin‐3‐O‐glucuronide PK suggests a minimal effect of sparsentan on metabolism of dapagliflozin by uridine 5′‐diphospho‐glucuronosyltransferase 1A9. No deaths, serious adverse events, or unusual safety signals occurred. Results suggest dapagliflozin PK is not affected by sparsentan daily dosing.