Safety Study of Cenderitide in Stable Chronic Heart Failure

Study Overview
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Brief Summary
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Planned enrollment is approximately twelve subjects with stable chronic heart failure. Enrolled subjects will receive up to eight sequential days of continuous, stepwise, dose increasing, subcutaneous (SQ) infusions of open-label cenderitide via the Insulet Drug Delivery System. Planned infusion rates of cenderitide will be administered to subjects continuously during four, 48-hour infusion periods.

Official Title
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A Study Assessing the Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Open-Label, Continuous, Stepwise, Dose Increasing, Subcutaneous Infusion of Cenderitide Via the Insulet Drug Delivery System in Subjects With Stable, Chronic Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Cenderitide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cenderitide<br>Cenderitide will be administered as four, 48-hour, continuous, subcutaneous infusion rates of 0.5, 1.0, 2.0 and 3.0 ng/kg/min totaling up to eight sequential days of dosing. | Drug: Cenderitide<br>* Cenderitide is a dual receptor natriuretic peptide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by changes in vital signs (blood pressure, heart rate, and body temperature), clinical laboratory tests, adverse events, 12-lead ECGs, and physical examinations compared to pre-dose, baseline measurements. |  | Measurements performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days). | 
| Pharmacokinetic (PK) profile of cenderitide as measured in area under the blood concentration-curve (AUC) from time zero to 48 hours post each infusion rate start, maximum blood concentration (Cmax), and time of maximum blood concentration (Tmax). |  | PK blood collection at regular intervals on Days 1-10. | 
| Pharmacodynamic (PD) response as assessed by changes in blood pressure, heart rate, weight, fluid balance (intake/output), plasma cGMP, ANP, NT-proBNP, and aldosterone, and urine cGMP compared to pre-dose baseline assessments. |  | PD assessments performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Heart Failure, Natriuretic Peptides, Cenderitide