Clinical trial NCT02359227: Safety Study of Cenderitide in Stable Chronic Heart Failure
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Chronic Heart Failure
Natriuretic Peptides
Cenderitide
Lead sponsor: Capricor Inc.
Sponsor class: INDUSTRY
First posted: 2015-02-09
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Measurements performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days).
measure: 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).
timeFrame: PK blood collection at regular intervals on Days 1-10.
measure: 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.
timeFrame: PD assessments performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days).
Secondary outcomes:
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
Study officials:
affiliation: Orange County Research Center
name: Joel Neutel, MD
role: PRINCIPAL_INVESTIGATOR
References: