Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 182-190, April 2009

Intravenous Recombinant Human Relaxin in Compensated Heart Failure: A Safety, Tolerability, and Pharmacodynamic Trial

  • Thomas Dschietzig, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • Corresponding Author InformationReprint requests: Thomas Dschietzig, Medizinische Klinik m. S. Kardiologie und Angiologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Schumannstr. 20/21, 10117 Berlin, Germany. Tel.: 0049-30-450 613 418; Fax: 0049-30-450 513 930.
    • ,
  • Sam Teichman, MD

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Elaine Unemori, MD

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Susy Wood

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Julia Boehmer

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Christoph Richter, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Gert Baumann, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Karl Stangl, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte

Received 17 September 2008; received in revised form 22 January 2009; accepted 28 January 2009. published online 09 March 2009.

Abstract 

Background

Relaxin is upregulated in human heart failure (HF). Animal and clinical data suggest beneficial hemodynamic and renal effects from vasodilation. We determined safety, tolerability, and pharmacodynamic effects of human Relaxin in stable HF.

Methods and Results

Sixteen patients were treated with open-label intravenous Relaxin in 3 dose-escalation cohorts and monitored hemodynamically for 24-hour infusion and postinfusion periods and followed until Day 30. The safety demonstrated in Group A (8-hour sequential infusions at dose levels of 10, then 30, and then 100 μg·kg·day equivalents) allowed escalation to Group B (240, 480, and 960 μg·kg·day). The highest safe dose, 960 μg·kg·day, was selected for a 24-hour infusion in Group C. Relaxin showed no adverse effects; produced hemodynamic effects consistent with vasodilation (ie, trends toward increases in cardiac index, decreases in pulmonary wedge pressure, and decreases in circulating NT-pro BNP without inducing hypotension; improved markers of renal function [creatinine, blood urea nitrogen]). The highest dose caused a transient elevation in creatinine and blood urea nitrogen at Day 9 that was without apparent clinical significance.

Conclusions

Relaxin was safe and well-tolerated in patients with stable HF, and preliminary pharmacodynamic responses suggest it causes vasodilation. Further evaluation of the safety and efficacy of this drug in HF appears warranted.

Key Words: Heart failure, vasodilation, peptide, hemodynamics

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 Sponsored by Corthera, Inc. S.T., E.U., and S.W. are employees of Corthera.

PII: S1071-9164(09)00030-X

doi:10.1016/j.cardfail.2009.01.008

Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 182-190, April 2009

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