Safety and Pharmacokinetics of a Novel Non-Steroidal Mineralocorticoid Receptor Antagonist, KBP-5074, in Hemodialysis and Non-Hemodialysis Patients with Severe Chronic Kidney Disease

Objective: KBP-5074 is a novel non-steroidal mineralocorticoid receptor antagonist for the potential treatment of hypertension. The purpose of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of 0.5 mg KBP-5074 in subjects with end stage renal disease on and not on hemodialysis. Results: Single doses of 0.5 mg KBP-5074 were generally well tolerated in both hemodialysis (N=6) and non-hemodialysis (N=5) subjects with severe renal impairment. Of the 11 subjects in the study, there was a single report of hyperkalemia in a hemodialysis subject on Day 14 that was not considered drug-related and was resolved in 2 days. Mean plasma KBP-5074 concentrations peaked at 6 and 4 hours in non-dialysis and dialysis subjects, respectively, and slowly declined through 312 hours postdose. Overall, the KBP-5074 exposures were significantly lower and had a shorter half-life in hemodialysis subjects compared with the non-hemodialysis subjects. However, hemodialysis had minimal direct impact on drug concentrations with negligible drug levels in the dialysate samples. Plasma aldosterone and serum potassium concentrations were generally comparable between non- hemodialysis and hemodialysis subjects, most likely to due to high variability in the hemodialysis subjects. Conclusion: The overall plasma exposure of KBP-5074 was statistically significantly lower in hemodialysis subjects compared to subjects with renal impairment not on hemodialysis.