Abstract
The effect of end-stage kidney disease (ESKD) and hemodialysis (HD) on avacopan exposure is unknown. This Phase 1 study evaluated the pharmacokinetics (PK) and safety of avacopan and its active metabolite M1 in healthy participants and participants with ESKD requiring HD following a single 30-mg oral dose administered with food. Healthy participants (N = 6) received one dose of avacopan, while participants with ESKD (N = 7) received a single 30-mg oral dose during each treatment period 18 days apart: once 4 h before HD and once on a non-HD day. PK parameters included area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC(last)), AUC from time 0-48 h (AUC(0-48)), and maximum concentration (C(max)). Comparisons were based on geometric least squares mean (GLSM) ratios with 90% confidence intervals. Relative to healthy participants, avacopan exposure on the non-HD day in participants with ESKD was similar, with GLSM ratios of 0.862 for AUC(0-48), 1.12 for AUC(last), and 1.03 for C(max). Corresponding M1 exposures were lower in participants with ESKD, with GLSM ratios ranging from 0.639 to 0.658. Within the ESKD group, avacopan exposure on the HD day was lower than on the non-HD day (GLSM ratios: 0.699-0.914), while M1 exposure was comparable between periods. Adverse events were mild to moderate and consistent with the known safety profile of avacopan. These findings indicate that ESKD or HD has no clinically meaningful impact on avacopan or M1 exposure, and dose adjustment may not be necessary in this population.