A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure

Rika Kawakami, Candace Y.W. Lee, Christopher Scott, Kent R Bailey, John A. Schirger, Horng Haur Chen, Sherry L. Benike, Valentina Cannone, Fernando L. Martin, S Jeson Sangaralingham, Tomoko Ichiki, John C Jr. Burnett

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cyclic GMP
Heart Failure
Safety
Natriuretic Peptides
C-Type Natriuretic Peptide
Peptide Receptors
Hypotension
cenderitide
Clinical Trials
Pharmacology
Blood Pressure
Kidney

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure. / Kawakami, Rika; Lee, Candace Y.W.; Scott, Christopher; Bailey, Kent R; Schirger, John A.; Chen, Horng Haur; Benike, Sherry L.; Cannone, Valentina; Martin, Fernando L.; Sangaralingham, S Jeson; Ichiki, Tomoko; Burnett, John C Jr.

In: Clinical Pharmacology and Therapeutics, 01.01.2018.

Research output: Contribution to journalArticle

@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 Haur} and Benike, {Sherry L.} and Valentina Cannone and Martin, {Fernando L.} and Sangaralingham, {S Jeson} and Tomoko Ichiki and Burnett, {John C Jr.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/cpt.974",
language = "English (US)",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure

AU - Kawakami, Rika

AU - Lee, Candace Y.W.

AU - Scott, Christopher

AU - Bailey, Kent R

AU - Schirger, John A.

AU - Chen, Horng Haur

AU - Benike, Sherry L.

AU - Cannone, Valentina

AU - Martin, Fernando L.

AU - Sangaralingham, S Jeson

AU - Ichiki, Tomoko

AU - Burnett, John C Jr.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85040549533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040549533&partnerID=8YFLogxK

U2 - 10.1002/cpt.974

DO - 10.1002/cpt.974

M3 - Article

C2 - 29226471

AN - SCOPUS:85040549533

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

ER -