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

The 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.