CONCLUSIONS
obesity, hepatic impairment, cirrhosis
OBESITY, HEPATIC IMPAIRMENT, CIRRHOSIS
This Phase Ib clinical trial examined the safety, tolerability, and PK of BI 685509, an sGC activator, in patients with CP-A or CP-B cirrhosis and HVs. This study demonstrated that multiple rising doses of BI 685509 were generally well tolerated in patients with mild or moderate hepatic impairment, with 3 serious AEs reported (all in patients with CP-B cirrhosis) and none considered to be drug-related. The PK and exposure of BI 685509 were similar between patient groups with mild (ie, CP-A) versus moderate (ie, CP-B) hepatic impairment and across different cirrhosis etiologies. Exposure of BI 685509 in matched HVs was lower compared with patients with hepatic impairment. While paired spleen stiffness measurements all decreased with BI 685509 treatment, the high failure rate of the technique, likely due to the prevalence of obesity in this population, limits this conclusion. The HepQuant SHUNT test results suggest that high doses of BI 685509 reduce portal–systemic shunting, indicating improved hepatic function. Thus, this trial supports further evaluation of BI 685509 for the treatment of patients with cirrhosis and PH.