Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects

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.

Figure 1

Structures and amino acid sequences of CNP, DNP, and CD-NP.

Figure 2

Plasma cGMP response (top left), urinary cGMP excretion (top right), natriuretic response (bottom left), and blood pressure response (bottom right). Mean ± SEM. Comparisons were made within (*P < .05, †P <.01) and between groups (“P < .01).

Figure 3

A plot of individual urinary sodium excretion (left panel, P < .05 vs baseline and P < .01 between groups) and urinary cGMP excretion (right panel, P < .01 vs baseline and P < .01 between groups) data. Mean ± SEM.