A Study Assessing The Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Subcutaneous Bolus And Subcutaneous Infusion Of Cenderitide In Patients With Chronic Heart Failure With Volume Overload (HF)

Inclusion Criteria:

- Male or female ≥ 18 years of age.

- Documented systolic heart failure with ejection fraction (EF) ≤ 40%

- Clinical evidence of volume overload

- Systolic blood pressure ≥ 120 mmHg and ≤ 200 mmHg and diastolic blood pressure > 60
mmHg and < 110 mmHg at the time of screening.

- Stable doses of oral medication at least 24 hours prior to screening

- No known allergy or contraindication to furosemide (Lasix®)

- Female patients must be post-menopausal or surgically sterile. A woman may be
considered to be surgically sterilized if she has had a bilateral tubal ligation (for
at least 6 months), bilateral oophorectomy or complete hysterectomy.

- Be adequately informed of the nature and risks of the study and give written informed
consent prior to receiving study medication.

Exclusion Criteria:

- Acute or suspected acute myocardial infarction (AMI) or troponin levels > 5X the
upper limit of normal at the institution's local laboratory and accompanied by
dynamic ECG changes consistent with AMI

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

- Evidence of uncorrected volume or sodium depletion (NA ≤ 130) or other condition that
would predispose the patient to adverse events.

- Clinically significant aortic or mitral valve stenosis.

- Temperature > 38°C (oral or equivalent), sepsis or active infection requiring IV
anti-microbial treatment.

- ADHF associated with significant arrhythmias (ventricular tachycardia,
bradyarrhythmias with ventricular rate < 45 beats per minute or atrial
fibrillation/flutter with ventricular response of > 160 beats per minute).

- Severe renal failure defined as creatinine clearance < 30 mL/min as estimated by both
the Cockcroft-Gault and the Modification of Diet in Renal Disease (MDRD) equations.

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

- Any organ transplant recipient, currently listed (anticipated in the next 60 days)
for transplant, or admitted for cardiac transplantation.

- Major surgery within 30 days.

- Major neurologic event, including cerebrovascular events in the prior 60 days.

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

- Known hepatic impairment

- Received an investigational drug within 30 days prior to screening.

- Women who are pregnant or breastfeeding.

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

- Any condition which, in the opinion of the Investigator, could interfere with, or for
which the treatment might interfere with the conduct of the study, or which would
unacceptably increase the risk of the patient's participation in the study.