@article{4249ef062a604a4f8c31ee7da0db5f71,
title = "A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure",
abstract = "Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic peptide (DNP). Cenderitide was engineered to coactivate the two NP receptors, particulate guanylyl cyclase (pGC)-A and -B. The rationale for its design was to achieve the renal-enhancing and antifibrotic properties of dual receptor activation, but without clinically significant hypotension. Here we report the first clinical trial on the safety, tolerability, and cyclic guanosine monophosphate (cGMP) activating properties of Cenderitide in subjects with stable heart failure (HF). Four-hour infusion of Cenderitide was safe, well-tolerated, and significantly increased plasma cGMP levels and urinary cGMP excretion without adverse effects with no change in blood pressure. Thus, Cenderitide has a favorable safety profile and expected pharmacological effects in stable human HF. Our results support further investigations of Cenderitide in HF as a potential future cGMP-enhancing therapeutic strategy.",
author = "Rika Kawakami and Lee, {Candace Y.W.} and Christopher Scott and Bailey, {Kent R.} and Schirger, {John A.} and Chen, {Horng H.} and Benike, {Sherry L.} and Valentina Cannone and Martin, {Fernando L.} and Sangaralingham, {S. Jeson} and Tomoko Ichiki and Burnett, {John C.}",
note = "Funding Information: This study was supported by grants from the National Institutes of Health: PO1 HL76611 (JCB) and RO1 HL36634 (JCB) and from the ASCPT (CYWL). We also acknowledge support from the Mayo Clinic NIH supported CTSA (UL1TR000135). Funding Information: This human study was designed as a randomized, double-blind, placebo-controlled trial to be conducted in subjects with stable chronic HF and reduced ejection fraction (EF) which was performed at the Clinical Research Unit (CRU) of the Mayo Clinic Center for Translational Science Activities (CTSA), Mayo Clinic, Rochester, MN. The study was supported by the National Heart, Lung, and Blood Institute (NHLBI). All subjects provided written, informed consent before enrollment. Study documentation was reviewed and approved by the Ethics Committee of the Mayo Clinic. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and its amendments, the US Food and Drug Administration Principles of Good Clinical Practice, and International Conference on Harmonization Guidelines, where applicable. The study was registered at ClinicalTrials.gov (ID: NCT00620308). Publisher Copyright: {\textcopyright} 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics",
year = "2018",
month = sep,
doi = "10.1002/cpt.974",
language = "English (US)",
volume = "104",
pages = "546--552",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "3",
}