Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability of ACT‐1014‐6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist

Abstract

AbstractThe aim of this study was to examine the safety and the effect of severe renal impairment (RI) on the pharmacokinetics of ACT‐1014‐6470, a novel oral complement factor 5a receptor 1 antagonist. A phase 1 single‐center, open‐label, single‐dose, parallel‐group study was conducted in subjects with severe RI (n = 8) compared to demographically pairwise matched subjects with normal renal function (n = 8). Plasma levels of ACT‐1014‐6470 were measured up to 120 hours following an oral 40‐mg dose. Safety evaluations included adverse events (AEs), vital signs, hematology, coagulation, clinical chemistry tests, and electrocardiograms. All 16 subjects completed the study. Relative to subjects with normal renal function, ACT‐1014‐6470 time to maximum plasma concentration was delayed with a median of differences of 3 hours. The maximum plasma concentration and the area under the plasma concentration–time profile from time zero to infinity were comparable indicated by geometric mean ratios (90%CI) of 0.85 (0.53–1.37) and 1.17 (0.73–1.85), respectively. Four transient and mild AEs in three subjects with severe RI were reported; three AEs were considered not related to ACT‐1014‐6470. These results support the use of ACT‐1014‐6470 in subjects with mild to severe RI without the need of dose adjustment.