The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of balcinrenone.

Abstract

Aims: The aim of this phase 1 trial was to assess the pharmacokinetics, safety and tolerability of balcinrenone (previously AZD9977) in participants with severe renal impairment vs. those with normal renal function.

Methods: Participants with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²) not on dialysis were compared with group-matched control participants with eGFR ≥ 90 mL/min/1.73 m². Eligible participants received a single oral dose of 150 mg balcinrenone, and blood and urine samples were collected for analysis.

Results: The total apparent balcinrenone clearance was 50% lower in the severe renal impairment group, resulting in an approximately two-fold higher area under the curve (AUC) and a 1.4-fold higher maximum observed plasma concentration in the severe renal impairment group compared with the control group. The terminal half-life and plasma protein binding were similar in both groups. Balcinrenone was safe and well tolerated in all participants. All reported adverse events were of mild-to-moderate severity and not considered related to balcinrenone.

Conclusions: Balcinrenone exposure was approximately two-fold higher in participants with severe renal impairment compared with the group-matched control participants. Based on linear regression analysis of total apparent balcinrenone clearance vs. baseline eGFR, the AUC exposure is predicted to be <50% higher in patients with an eGFR of 20 mL/min/1.73 m² compared with those with an eGFR of 60 mL/min/1.73 m². In light of these findings, no dose adjustment based on eGFR is needed in two ongoing studies that target these patients (MIRO-CKD [NCT06350123] and BalanceD-HF [NCT06307652]).