Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO‐DKD and FIDELIO‐DKD

• DOI: 10.1111/dom.15387
• Publication Date: 2023-12-01T07:03:29Z
• Authors: Thomas Eissing; Sebastiaan Camiel...; Paul van den Berg; Martijn van Noort; Martijn Ruppert; Nelleke Snelder; Dirk Garmann; Joerg Lippert; Roland Heinig; Meike Brinker; Hiddo J. L. Heers...
• Keywords: Pharmacodynamics

Abstract Aims To perform dose–exposure–response analyses to determine the effects of finerenone doses. Materials and Methods Two randomized, double‐blind, placebo‐controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each an estimated glomerular filtration rate (eGFR) 25 90 mL/min/1.73 m , a urine albumin‐creatinine ratio (UACR) 30 5000 mg/g, serum potassium ≤ 4.8 mmol/L were included. Interventions titrated doses 10 or 20 mg versus placebo on top standard care. The outcomes trajectories plasma concentrations, UACR, eGFR kidney composite outcomes, assessed using nonlinear mixed‐effects population pharmacokinetic (PK)/pharmacodynamic (PD) parametric time‐to‐event models. Results For potassium, lower levels rates hyperkalaemia associated higher compared ( p < 0.001). PK/PD model analysis linked this observed inverse association potassium‐guided dose titration. Simulations hypothetical trial constant revealed shallow but increasing exposure–potassium response relationship. Similarly, exposures led less than dose‐proportional reductions in modelled UACR. Modelled UACR explained 95% finerenone's treatment effect slowing chronic decline. No UACR‐independent identified. Neither sodium‐glucose cotransporter‐2 (SGLT2) inhibitor nor glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) significantly modified reducing 87% outcomes. eGFR‐independent Conclusions provide strong evidence for effectiveness titration controlling elevations. are predictive during treatment. Finerenone's efficacy is independent concomitant use SGLT2 inhibitors GLP‐1RAs.