ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO241

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist KBP-5074 in Individuals With Moderate Hepatic Impairment

Session Information

  • Pharmacology
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

  • 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

Authors

  • McCabe, James Carden, Kbp Biosciences Co Ltd, Jinan, China
  • Benn, Vincent, Kbp Biosciences Co Ltd, Jinan, China
  • Zhang, Jay, Kbp Biosciences Co Ltd, Jinan, China
  • Yang, Y. Fred, Kbp Biosciences Co Ltd, Jinan, China
Background

KBP-5074 is a selective nonsteroidal mineralocorticoid receptor antagonist. This study assessed the effect of moderate hepatic impairment on the pharmacokinetics, safety, and tolerability of KBP-5074.

Methods

This was an open, nonrandomized, multicenter, study investigating the PK, safety, and tolerability of a single oral dose of 0.5 mg KBP-5074 to male and female subjects with moderate hepatic impairment (Child-Pugh B score 7-9) compared to normal healthy subjects. Twelve subjects (6 subjects with moderate impairment and 6 matched healthy control subjects) were enrolled. All subjects received a single oral dose of 0.5 mg KBP-5074 on Day 1 after an overnight fast of ≥10 hours. Each healthy control subject was matched by age (±10 years), BMI (±20%), and sex to a moderate hepatic impairment subject. Serial blood collections were obtained through 264 hours postdose for plasma levels of KBP-5074. Plasma protein binding was analyzed and safety and tolerability were monitored.

Results

Following a single oral dose of 0.5 mg, KBP-5074 was steadily absorbed with median Tmax values of 4.00 and 3.00 hours, respectively. After reaching Cmax, the disposition of KBP-5074 appeared to be biphasic. The geometric mean t1/2 values for the moderate hepatic impairment group and normal healthy control group were 75.6 and 65.7 hours, respectively. Systemic exposure to KBP-5074 as assessed by AUC was 23.5% to 26.6% lower in subjects with moderate hepatic impairment versus healthy subjects, whereas Cmax was 41.2 % lower. KBP-5074 was determined to be >99.7% bound to proteins in plasma. Given the low percentage of unbound drug, it was not deemed appropriate to calculate the PK parameters for unbound drug. KBP-5074 was safe and well tolerated in all participants.

Conclusion

Small decreases of AUC and Cmax upon systemic exposure to KBP-5074 in subjects with moderate hepatic impairment demonstrate low hepatic extraction and is consistent with the observation that KBP-5074 is cleared predominantly in the gastrointestinal tract vs the kidney.
Considering the long half-life and small decrease in AUC and Cmax, a dose adjustment does not appear to be warranted in patients with moderate hepatic impairment.

Funding

  • Commercial Support