Kobalava, Zhanna, Villevalde, Svetlana, Svetlana, Yulia, Hinrichsen, Holger, Marc, Petersen-Sylla, Zaehringer, Andreas, Pang, Yinuo, Rajman, Iris, Canadi Semadeni, Jasna, Dahlke, Marion, Lloyd, Peter and Halabi, Atef (3276) Pharmacokinetics of serelaxin in patients with hepatic impairment: A single-dose, open-label, parallel-group study. British Journal of Clinical Pharmacology, 79 (6). pp. 937-945. ISSN 03065251

Abstract

AIMS
Serelaxin is a recombinant form of human relaxin-2 in development for the treatment of acute heart failure. The present study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included the evaluation of immunogenicity, safety and tolerability of serelaxin.
METHODS
This was an open-label, parallel-group study (NCT01433458) comparing the PK of serelaxin following a single 24-hour intravenous (IV) infusion (30 μg/kg/day) between patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B and C, respectively), 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)0-48h and AUCinf, and serum concentration at 24 hours post-dose (C24h)] 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, serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 hours and then declined following completion of the infusion with a mean terminal half-life of 7-8 hours. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to an adverse event 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-hr IV infusion in patients with hepatic impairment.

Item Type:	Article
Keywords:	cardiovascular disease, healthy subjects, hepatic, pharmacokinetics, therapeutics
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24104