Abstract 12961: No Effect of Hepatic Impairment on the Pharmacokinetics of Serelaxin, a Recombinant Human Relaxin-2 in Development for the Treatment of Acute Heart Failure
Introduction: The RELAX-AHF (Relaxin in Acute Heart Failure [AHF]) Phase lll study (NCT00520806) examined the effects of serelaxin (recombinant human relaxin-2) in patients with AHF, and demonstrated favorable tolerability with benefits on short- and longer-term outcomes. The present study evaluated the effect of hepatic impairment on serelaxin pharmacokinetics (PK). Secondary study objectives included safety, tolerability, and immunogenicity of serelaxin.
Methods: This open-label, parallel-group study (NCT01433458) enrolled patients 18-70 years of age (mean age 52.0; SD 8.8) with mild (n=9), moderate (n=8), or severe (n=8) hepatic impairment (Child-Pugh Class A, B, and C, respectively) and matched healthy volunteers (n=24). All subjects received a single 24h IV infusion of serelaxin 30 μg/kg/day. Blood sampling and standard safety assessments were conducted. Noncompartmental PK parameters were estimated based on the serelaxin serum concentration-time profiles. Primary PK parameters [including area under the plasma concentration-time curve (AUC)0-48h and AUCinf, and serum concentration 24h post-dose (C24h)] were compared between each hepatic impairment group versus healthy subject controls to evaluate the potential impact of hepatic impairment on serelaxin PK.
Results: PK profiles in subjects with varying severity of hepatic impairment were similar to those in subjects with normal hepatic function (Table 1). No deaths, serious adverse events (AEs), discontinuations due to an AE, or clinically significant changes in laboratory parameters or vital signs were reported. No subject developed anti-serelaxin antibodies by the end of the study (Day 15 of follow-up).
Conclusions: Hepatic impairment (Child-Pugh Class A-C) did not affect the PK and safety profile of serelaxin, indicating that dose adjustment is unlikely to be required for such patients.
Supported by Novartis Pharma AG.
- © 2013 by American Heart Association, Inc.