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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- 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).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Cenderitide
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.
干预措施: Cenderitide (Drug)
结局指标
主要结局
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).
时间窗: 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.
时间窗: PD assessments performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days).
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.
时间窗: Measurements performed at regular intervals on Days 1-10, and at the safety follow-up visit (Day 16 ± 2 days).
次要结局
未报告次要终点