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Abstract: SA-PO639

Safety, Tolerability, and Pharmacokinetics of the Selective Mineralocorticoid Receptor Antagonist KBP-5074 in Hemodialysis and Non-Hemodialysis Patients with Severe CKD

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Connaire, Jeffrey J., Davita Clinical Research, Minneapolis, Minnesota, United States
  • Bush, Mark A, Wingate University School of Pharmacy, Wingate, North Carolina, United States
  • Benn, Vincent, KBP Biosciences USA Inc, Princeton, New Jersey, United States
  • Yang, Y. Fred, KBP Biosciences Co., Ltd., Princeton, New Jersey, United States
  • Ruckle, Jon Leslie, Pacific Pharma Group, LLC, Tacoma, Washington, United States
  • Tan, Xiaojuan, KBP Biosciences Co., Ltd., Princeton, New Jersey, United States
Background

Background: Chronic kidney disease (CKD) is a leading cause of morbidity/mortality in the US. Mineralocorticoid receptor antagonism (MRA) has been shown to benefit in heart failure/hypertension but not in advanced CKD patients due to safety concerns, e.g., hyperkalemia. KBP-5074 is a novel, non-steroidal, highly-selective MRA being developed for patients with hypertension and advanced CKD.

Methods

Methods: This was a Phase 1, open-label study to evaluate the safety, tolerability, and pharmacokinetics (PK) of KBP-5074 following single oral administration to subjects with severe CKD, comparing Stage 5 subjects receiving hemodialysis (HD) with Stage 4 subjects not receiving hemodialysis (non-HD). Eleven subjects (6 HD and 5 non-HD) were enrolled and received a single 0.5 mg dose of KBP-5074. HD subjects were dosed immediately following a dialysis session. All subjects were followed for 13 days post-dose. In HD subjects, PK samples were collected before, during, and after the first HD session.

Results

Results: The mean age of the study subjects was 53.5 years; 54.5% were male. KBP-5074 was well tolerated: 6 TEAEs (mostly mild) were reported in 4/11 subjects. Plasma exposure of KBP-5074 in HD subjects was statistically significantly lower than in non-HD subjects: Cmax (7.34 ng/ml vs 10.6 ng/ml)/AUC (669 hr*ng/ml vs. 1310 hr*ng/ml), and T1/2 was shorter in HD subjects (64.2 hrs vs. 87.9 hrs). HD was associated with minimal alterations in KBP-5074 plasma concentrations and outflow dialysate concentrations of KBP-5074 were undetectable, indicating negligible clearance of KBP-5074 via HD. Plasma aldosterone and serum potassium values were generally comparable between HD and non-HD subjects.

Conclusion

Conclusions: KBP-5074 at a dose of 0.5 mg was safe and well tolerated in all study subjects. Plasma exposures of KBP-5074 in HD subjects were significantly lower than in non-HD subjects. Hemodialysis had a negligible effect on plasma concentrations of KBP-5074. These data support further evaluation of KBP-5074 in patients with advanced CKD.

Funding

  • Commercial Support