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Abstract: FR-PO218

Pharmacokinetics and Drug-Drug Interaction of KBP-5074 in Healthy Subjects

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

  • Wang, Ping, Kbp Biosciences Co Ltd, Jinan, China
  • Jinrong, Liu, Kbp Biosciences Co Ltd, Jinan, China
  • Tan, Judy, Kbp Biosciences Co Ltd, Jinan, China
  • Zhang, Jay, Kbp Biosciences Co Ltd, Jinan, China
  • Yang, Y. Fred, Kbp Biosciences Co Ltd, Jinan, China
  • McCabe, James Carden, Kbp Biosciences Co Ltd, Jinan, China
Background

KBP-5074, a selective nonsteroidal MRA inhibitor, has a favorable safety profile and significant activity on hypertension and nephropathy in stage 3/4 CKD patients with uncontrolled hypertension. A clinical DDI study was conducted in healthy volunteers to evaluate the effect of a CYP3A4 inhibitor and inducer on the PK of KBP-5074.

Methods

This was a phase 1 study to investigate the effect of coadministration of a CYP3A4 inhibitor (itraconazole) and CYP3A4 inducer (rifampin) on the plasma PK of a single dose of KBP-5074 in healthy male and female subjects. 24 subjects 18 to 60 years of age with a BMI of 18.0 to 32.0 kg/m2 were selected. Serial blood collections were obtained from pre-dose through 240 hours post-dose for analysis of plasma concentrations of KBP-5074.

Results

The strong CYP3A inhibitor itraconazole and strong CYP3A inducer rifampin had statistically significant effects on the pharmacokinetics of KBP-5074. The exposures were 1.1 fold and 1.7 fold higher when KBP-5074 was administered in combination with itraconazole based on Cmax and AUClast. The median tmax was reduced (from 4 h to 2h) and geometric mean t1/2 was longer (60.3 h to 125 h) in the presence of itraconazole. When KBP-5074 was administered in combination with rifampin, exposures were decreased approximately 28% and 84% based on Cmax and AUClast. Median tmax was similar (4 hours), but geometric mean t1/2 was shorter (10.9 hours).

Conclusion

A strong CYP3A inhibitor (itraconazole) had a weak effect (1.1 to 1.7 fold increase), whereas a strong CYP3A4 inducer (rifampin) had a strong effect (up to 84% decrease) on the clinical pharmacokinetics of KBP-5074. KBP-5074 was well tolerated when administered as a single 0.5-mg dose alone or in combination with itraconazole or rifampin.

Funding

  • Commercial Support