Safety Study of Cenderitide in Stable Chronic Heart Failure

Key Inclusion Criteria:

- Male or female, ≥ 18 years of age

- Body Mass Index (BMI) of 18-40 kg/m2, inclusive

- Current or historical New York Heart Association (NYHA) functional class ≥ II

- At least one of the following: documented systolic heart failure with an ejection
fraction (EF) ≤ 40% and/or a historical measurement of plasma BNP ≥ 150 pg/mL (or
NT-proBNP ≥ 600 pg/mL)

- Systolic blood pressure 100-160 mmHg

- Stable and compliant treatment with oral heart failure medications for at least 4
weeks prior to Screening

Key Exclusion Criteria:

- Known hypersensitivity or allergy to natriuretic peptide or its components,
nesiritide, other natriuretic peptides or related compounds

- Current clinical diagnosis of acute decompensated heart failure (ADHF)

- Clinical diagnosis of acute coronary syndrome (ACS) within 30 days prior to Screening.

- Symptomatic postural hypotension

- Evidence of uncorrected volume or sodium ≤ 130 mmol/L or other condition that would
predispose the patient to adverse events

- Clinically significant aortic or mitral valve stenosis

- Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive
cardiomyopathy (not including restrictive mitral filling patterns)

- Severe renal failure defined as creatinine clearance < 45 mL/min as estimated by
either the Cockcroft-Gault or the MDRD equations

- Significant pulmonary disease (e.g., history of oral daily steroid dependency, history
of Carbon Dioxide (CO2) retention or need for intubation for acute exacerbation, or
currently receiving IV steroids)

- Known hepatic impairment as indicated by any of the following: A) total bilirubin > 3
mg/dL; B) albumin < 2.8 mg/dL, with other signs or symptoms of hepatic dysfunction; C)
increased ammonia levels, if performed, with other signs or symptoms of hepatic
dysfunction