The effect of mild and moderate hepatic impairment on the pharmacokinetics, safety and tolerability of balcinrenone.

AIM: Balcinrenone (previously AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist (MRA) with a differential mechanism of action relative to approved MRAs. The aim of this trial was to assess the pharmacokinetics, safety and tolerability of balcinrenone in participants with mild and moderate hepatic impairment versus participants with normal hepatic function.

METHODS

Participants with mild and moderate hepatic impairment (Child-Pugh Class A [n = 8] and Child-Pugh Class B [n = 8]) were compared with group matched controls with normal hepatic function [n = 9]. Eligible participants received a single oral dose of 50-mg balcinrenone. Blood and urine samples were collected. Safety and tolerability were monitored.

RESULTS

In participants with mild hepatic impairment, balcinrenone exposure (area under the plasma concentration-time curve [AUC] and maximum plasma concentration [Cmax]) was similar compared with participants with normal hepatic function. In participants with moderate hepatic impairment, Cmax was similar, but there was a slight and statistically significant 30% (90% CI 4%-61%) increase in AUC compared with participants with normal hepatic function. Balcinrenone was well tolerated. All reported adverse events were of mild to moderate intensity.

CONCLUSIONS

Compared with participants with normal hepatic function, balcinrenone exposure was similar in participants with mild hepatic impairment. AUC, but not Cmax, was slightly increased in participants with moderate hepatic impairment. We do not consider the minor AUC increase seen in participants with moderate hepatic impairment to be clinically relevant. Thus, we would not recommend any dose adjustment for patients with mild or moderate hepatic impairment.