A Randomized, Double-Blind, Placebo-Controlled Parallel Arm Study to Evaluate the Safety, Tolerability, and Effect on Atrial Fibrillation Burden of BMS-919373 in Patients With Paroxysmal Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 158
- 试验地点
- 25
- 主要终点
- Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System
研究概览
简要总结
The purpose of this study is to evaluate the effect of BMS-919373 on atrial fibrillation (AF) through its effect on AF burden (AFB), or the percent of time in AF, in subjects with paroxysmal AF (pAF) when administered orally at a range of doses (2 mg once daily (QD), 5 mg QD, 12 mg QD following a 1-week period of loading doses of 3 mg QD, 8 mg QD and 20 mg QD, respectively) for a total of 4 weeks. It is hypothesized that treatment with BMS-919373 will reduce AF burden as compared to baseline relative to placebo.
详细描述
Primary Purpose: Protocol designed to assess, by the use of long term non-invasive beat-to-beat monitoring with the SEEQ Mobile Cardiac Telemetry (MCT) system, the effect of BMS-919373 on the percent change from baseline relative to placebo of atrial fibrillation burden in subjects with paroxysmal atrial fibrillation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Paroxysmal Atrial Fibrillation (pAF) with available documentation of AF and reporting symptoms within 6 months prior to screening
- •Able to tolerate withdrawal of antiarrhythmic therapy (rhythm control)
- •Echocardiographically measured left ventricular ejection fraction (LVEF) ≥40%,measured within 12 months of enrollment
- •Echocardiographically measured left atrial (LA) diameter ≤ 5.0 cm, measured within 12 months of enrollment
排除标准
- •Women of childbearing potential
- •AFB < 3% or > 70%, during both screening periods independently
- •Permanent or persistent Atrial Fibrillation
- •Cardioversion within 3 months of study drug administration
- •Stroke within 12 months of study drug administration
- •TIA within 12 months of study drug administration
- •Heart failure of NYHA class III or greater (symptoms of heart failure at rest or with minimal exertion)
- •Heart failure of NYHA class II (symptoms of heart failure with routine levels of exertion)with ejection fraction <40% as measured by echocardiography at any time within 12 months of study enrollment (i.e. additional ejection fraction measurements ≥ 40% over this period will not counter this exclusion)
- •Valvular heart disease (including any valvular insufficiency or stenosis greater than"mild")
- •Ablation within 3 months of study enrollment
研究组 & 干预措施
Arm A: Placebo (Matching with BMS-919373)
Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days
干预措施: Placebo (Matching with BMS-919373) (Drug)
Arm B: BMS-919373
BMS-919373 3 mg tablets orally once daily for approximately 28 days
干预措施: BMS-919373 (Drug)
Arm C: BMS-919373
BMS-919373 5 mg tablets orally once daily for approximately 28 days
干预措施: BMS-919373 (Drug)
Arm D: BMS-919373
BMS-919373 12 mg tablets orally once daily for approximately 28 days
干预措施: BMS-919373 (Drug)
结局指标
主要结局
Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System
时间窗: Day 8 to Day 29
AFB is defined as the percent of time spent in atrial fibrillation (AF). AFB will be assessed by use of long term non- invasive beat-to-beat monitoring with the SEEQ MCT system. This technology consists of a low-profile adhesive patch that has been approved for continuous use for up to 30 days. The patch is able to continuously record electrocardiographic signals and, in conjunction with a wirelessly connected portable cellular communications device, transmit these signals for real-time analysis, including atrial and ventricular arrhythmias and AFB.
次要结局
- Maximum Observed Concentarion (Cmax) of BMS-919373(Day 1 and Day 22: Predose 1, 2, and 4 hours postdose)
- Average Concentration (Cavg) of BMS-919373 at Steady State(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))
- Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))
- Time to First Atrial Fibrillation Recurrence (TTFR) (Symptomatic or Asymptomatic)(Day 8 to Day 29)
- Total Number of Atrial Fibrillation Episodes(Day 8 to Day 29)
- Average Duration of Atrial Fibrillation Per Episode(Day 8 to Day 29)
- Trough Observed Concentration (Cmin) of BMS-919373(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death(Up to Day 50)
- Central Volume of Distribution (Vc/F) of BMS-919373(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))
- Oral Clearance (CL/F) of BMS-919373(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))
- Absorption Rate Constant (Ka) of BMS-919373(Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28))