A Randomized, Double-Blind, Placebo-Controlled, Cross-over Phase 2 Study of Continuous 8-Hour Intravenous Infusions of BMS-986231 in Patients With Heart Failure and Impaired Systolic Function Given a Standard Dose of Loop Diuretic
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo
研究概览
简要总结
The purpose of this study is to investigate continuous 8-hour introductions of BMS-986231 in participants with heart failure and weakened heart function given a standard dose of diuretic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Left ventricular ejection fraction <45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan within 18 months
- •On stable chronic guideline-directed therapy for HF including chronic loop diuretics, ACEi, ARBs, MRAs, ARNI or / and β-blockers as tolerated, with no changes of these medications in the past 2 weeks
- •At least an oral dose of 40 mg of furosemide/day or equivalent (20 mg torsemide, 1 mg bumetamide)
排除标准
- •SBP < 115 mm Hg or > 180 mm Hg at screening or pre-randomization
- •Heart rate < 50 beats per minute (bpm) or > 120 bpm at screening or pre-randomization
- •Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Placebo+Diuretic to BMS-986231+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: BMS-986231 (Drug)
Placebo+Diuretic to BMS-986231+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: Furosemide (Drug)
Placebo+Diuretic to BMS-986231+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: Placebo (Drug)
BMS-986231+Diuretic to Placebo+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: BMS-986231 (Drug)
BMS-986231+Diuretic to Placebo+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: Furosemide (Drug)
BMS-986231+Diuretic to Placebo+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
干预措施: Placebo (Drug)
结局指标
主要结局
4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo
时间窗: 4 hours
The total volume of urinary output 4 hours after 40 mg furosemide bolus given to participants with HFrEF while on BMS-986231 compared to placebo: absolute difference in total volume and % change from placebo. Sequence 1: Placebo in period 1, drug in period 2 Sequence 2: Drug in period 1, placebo in period 2
次要结局
- Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion(0-4 hours after furosemide)
- Number of Participants With an Adverse Event (AE)(up to 8 days)
- Change From Baseline in Vital Signs - Blood Pressure(Day 1, 8 hours post-dose (end of infusion))
- FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo(Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours)
- Furosemide Plasma Concentrations(Day 1: 4, 5, 6, 8, 10 hours)
- Number of Participants With Clinically Relevant Hypotension(up to 8 hours)
- Number of Participants With an Abnormal Clinical Laboratory Value(from first dose to 30 days post-last dose (ca. 5-8 weeks))
- FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo(Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours)
- Furosemide Urinary Concentrations(Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours)
- Change From Baseline in Vital Signs - Heart Rate(Day 1, 8 hours post-dose (end of infusion))
- Change From Baseline in Vital Signs - Oxygen Saturation(Day 1, 8 hours post-dose (end of infusion))
- Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate(Day 1, 8 hours post-dose (end of infusion))
- Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals(Day 1, 8 hours post-dose (end of infusion))
- Telemetry(Day 1, 8 hours post-dose)
- Change From Baseline in Physical Examination - Body Weight(Day 1, 8 hours post-dose (end of infusion))