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]).