NCT05139615终止2 期
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of APD418 in Subjects With Heart Failure With Reduced Ejection Fraction
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 22
- 试验地点
- 21
- 主要终点
- Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics, and effect on cardiac function of intravenous APD418 in adult participants with heart failure with reduced ejection fraction (HFrEF).
详细描述
This study has an adaptive design, in which dose escalation in Part A will inform dose expansion in Part B. Part A is a single-ascending dose, placebo-controlled study planned to consist of 5 cohorts evaluating 5 doses of APD418. Part B is a parallel-treatment group study planned to evaluate 2 doses of APD418 and placebo. Participants in Part A cannot participate in Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced chronic Heart Failure with Reduced Ejection Fraction (HFrEF), defined as left ventricular ejection fraction (LVEF) less than or equal to (≤) 35% at Screening, including documented history of HFrEF (LVEF ≤ 35%) for at least 4 months prior to Screening
- •New York Heart Association Class II-IV
- •Cardiac index ≤ 2.5 liters per minute per square meter (L/min/m^2) and pulmonary capillary wedge pressure ≥ 15 millimeters of mercury (mm Hg) at Day 1
- •Body mass index 18.0 to 37.0 kilograms per square meter (kg/m^2), inclusive, and body weight < 150 kg at Screening and Day 1
排除标准
- •Hemodynamically unstable at Day 1 or in the opinion of the Investigator likely to progress to becoming hemodynamically unstable during the course of the study
- •Treated with carvedilol or at a dose higher than a total of 25 milligrams per day any time within 72 hours of Day 1 through the end of the in-clinic observation Post-dose Period.
- •Receiving any mechanical (respiratory or circulatory) or renal support therapy at Screening or Day 1
- •Systolic Blood Pressure ≤ 90 millimeter of mercury (mm Hg) or ≥ 160 mm Hg, or Heart Rate < 50 beats per minute (bpm) or > 110 bpm, at Screening or Day 1
- •Recently treated with inotropic, intravenous (IV) vasoactive or IV diuretic therapy, or expected to require such therapy with these drugs any time from Day 1 through the end of study conduct.
研究组 & 干预措施
APD418 (Part B: Dose Group 1 and 2)
Experimental
干预措施: APD418 (Drug)
APD418 (Part A: Dose Cohort 1-5)
Experimental
干预措施: APD418 (Drug)
Placebo (Part A: Cohort 1-5 and Part B)
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours
时间窗: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)
Cardiac index (CI) is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA), thus relating heart performance to the body size of the participant. It was measured by RHC.
次要结局
- Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4 and 5 hours of IV infusion)
- Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours(Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion))
- Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Terminal Elimination Half-Life (t1/2) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours(Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion)
- Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From start of study treatment on Day 1 up to Day 9)
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start)
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Maximum Observed Plasma Concentration (Cmax) of APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Distributional Half-Life (t1/2a) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Total Clearance (CL) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Volume of Distribution at Steady State (Vdss) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start)
- Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start)
- Part A: Renal Clearance (CLr) for ADP418(Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals)
研究者
研究点 (21)
Loading locations...
相似试验
已完成
2 期
TNP-2092 to Treat Acute Bacterial Skin and Skin Structure InfectionSkin and Subcutaneous Tissue Bacterial InfectionsGram-Positive Bacterial InfectionsNCT03964493TenNor Therapeutics Limited120
已完成
2 期
Study Evaluating Intravitreal hI-con1™ in Patients With Choroidal Neovascularization Secondary to Age-related Macular DegenerationAge-related Macular DegenerationChoroidal NeovascularizationNCT02358889Iconic Therapeutics, Inc.88
已完成
2 期
Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR MutationCystic FibrosisNCT01225211Vertex Pharmaceuticals Incorporated312
撤回
3 期
A Study of Meropenem-Vaborbactam Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired and Ventilator-Associated Bacterial PneumoniaHospital-Acquired Bacterial PneumoniaVentilator-Associated Bacterial PneumoniaHospital-Acquired PneumoniaVentilator-Associated PneumoniaNCT03006679Melinta Therapeutics, Inc.
已完成
2 期
Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With SchizophreniaSchizophreniaNCT05278156Celon Pharma SA189