Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose,open-label,parallel group study

Aims

Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin.

Methods

This was an open-label, parallel group study ({"type":"clinical-trial","attrs":{"text":"NCT01433458","term_id":"NCT01433458"}}NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg⁻¹ day⁻¹) between patients with mild, moderate or severe hepatic impairment (Child–Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration–time curve AUC(0–48 h) and AUC(0–∞) and serum concentration at 24 h post-dose (C_24h)] were compared between each hepatic impairment group and healthy controls.

Results

A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12–24 h and then declined following completion of infusion, with a mean terminal half-life of 7–8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study.

Conclusions

The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.