Pharmacodynamics Pharmacodynamics of a Novel Designer Natriuretic Peptide, CD-NP, in a First-in-Human Clinical Trial in Healthy Subjects

Authors

  • Dr Candace Y. W. Lee MD, PhD, FCP,

    1. Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Departments of Medicine and Physiology, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
    2. Division of Clinical Pharmacology, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
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  • Dr Horng H. Chen MB, BCh,

    1. Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Departments of Medicine and Physiology, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
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  • Dr Ondrej Lisy MD, PhD,

    1. Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Departments of Medicine and Physiology, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
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  • Dr Suzanne Swan MD,

    1. DiVita Clinical Research, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
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  • Ms Courtney Cannon,

    1. DiVita Clinical Research, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
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  • Dr Hsiao D. Lieu MD,

    1. Nile Therapeutics, Inc, San Francisco, California
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  • Dr John C. Burnett Jr. MD

    Corresponding author
    1. Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Departments of Medicine and Physiology, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
    2. Division of Clinical Pharmacology, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
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Address for correspondence: John C. Burnett, Jr, MD, Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905;e-mail: burnett.john@mayo.edu.

Abstract

CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate—activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now underway worldwide.

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