A Phase 1, Two-Part, Double-blind, Placebo-controlled, Randomized Study of the Safety, Tolerability, and Pharmacokinetics of BMS-986278 (Part A) and a Randomized, Double-blind, Positive-controlled, Placebo-controlled, 4-Period Crossover, Thorough QT/QTc Study to Evaluate the Effect of Multiple Doses of BMS-986278 on Cardiac Repolarization (Part B) in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Number of participants with non-serious Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and pharmacokinetics (PK) of high dose of BMS-986278 in healthy participants and to assess the effect of BMS-986278 on the ECG intervals in healthy participants.
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)
盲法说明
This is a double-blind study, with an open-label positive control in Part B.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female individuals not of childbearing potential (INOCBP) and males.
- •Healthy as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory assessments.
- •Body mass index (BMI) 18.0 to 32.0 kg/m2 , inclusive, for Parts A and B.
排除标准
- •Any significant acute or chronic medical illness as determined by the investigator.
- •History of clinically relevant cardiac disease as determined by the investigator, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for ventricular arrhythmias.
- •Any significant history of disease of the cardiovascular system that in the opinion of the Investigator makes the participant unsuitable for enrollment into the study.
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part A
干预措施: BMS-986278 (Drug)
Part A
干预措施: Placebo (Drug)
Part B1/B2 Treatment A
干预措施: BMS-986278 (Drug)
Part B1/B2 Treatment B
干预措施: BMS-986278 (Drug)
Part B1/B2 Treatment B
干预措施: Placebo (Drug)
Part B1/B2 Treatment C
干预措施: Placebo (Drug)
Part B1/B2 Treatment D
干预措施: Placebo (Drug)
Part B1/B2 Treatment D
干预措施: Moxifloxacin (Drug)
Part B3 Treatment A
干预措施: BMS-986278 (Drug)
Part B3 Treatment B
干预措施: BMS-986278 (Drug)
Part B3 Treatment B
干预措施: Placebo (Drug)
Part B3 Treatment C
干预措施: Placebo (Drug)
Part B3 Treatment D
干预措施: Placebo (Drug)
Part B3 Treatment D
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Number of participants with non-serious Adverse Events (AEs)
时间窗: Until 28 days post last treatment dose
Part A
Number of participants with Serious AEs (SAEs)
时间窗: Until 28 days post last treatment dose
Part A
Number of participants with AEs leading to study intervention discontinuation
时间窗: Until 28 days post last treatment dose
Part A
Number of participants with vital sign abnormalities
时间窗: Up to Day 18
Part A
Number of participants with clinical laboratory assessment abnormalities
时间窗: Up to Day 18
Part A
Number of participants with 12-lead electrocardiogram (ECG) abnormalities
时间窗: Up to Day 18
Part A
Number of participants with physical examination abnormalities
时间窗: Up to Day 18
Part A
Change from baseline Fridericia's corrected QT interval (QTcF) (ΔQTcF)
时间窗: Up to Day 13 of Period 4 (Each period is 17 days)
Part B
Placebo-corrected change from baseline QTcF (ΔΔQTcF)
时间窗: Up to Day 13 of Period 4 (Each period is 17 days)
Part B
次要结局
- Maximum observed plasma concentration (Cmax)(Up to Day 13 of Period 4 (Each period is 17 days))
- Time of maximum observed plasma concentration (Tmax)(Up to Day 13 of Period 4 (Each period is 17 days))
- Area under the plasma concentration-time curve from time zero to the end of dosing interval AUC(TAU)(Up to Day 13 of Period 4 (Each period is 17 days))
- Terminal half-life (T-HALF)(Up to Day 18)
- Apparent total body clearance (CLT/F)(Up to Day 18)
- Change from baseline heart rate (HR) (∆HR)(Up to Day 13 of Period 4 (Each period is 17 days))
- Change from baseline PR interval (∆PR)(Up to Day 13 of Period 4 (Each period is 17 days))
- Change from baseline QRS interval (∆QRS)(Up to Day 13 of Period 4 (Each period is 17 days))
- Placebo-corrected change from baseline HR (ΔΔHR)(Up to Day 13 of Period 4 (Each period is 17 days))
- Placebo-corrected Change from baseline PR interval (ΔΔPR)(Up to Day 13 of Period 4 (Each period is 17 days))
- Placebo-corrected change from baseline QRS interval (ΔΔQRS)(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with categorical outliers for QTcF(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with categorical outliers for HR(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with categorical outliers for PR interval(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with categorical outliers for QRS interval(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with treatment-emergent changes of ECG morphology(Up to Day 13 of Period 4 (Each period is 17 days))
- ΔQTcF for moxifloxacin(Up to Day 13 of Period 4 (Each period is 17 days))
- ΔΔQTcF for moxifloxacin(Up to Day 13 of Period 4 (Each period is 17 days))
- Number of participants with non-serious AEs(Until 28 days post last treatment dose)
- Number of participants with SAEs(Until 28 days post last treatment dose)
- Number of participants with AEs leading to study intervention discontinuation(Until 28 days post last treatment dose)
- Number of participants with vital sign abnormalities(Up to Day 18 of Period 4 (Each period is 17 days))
- Number of participants with clinical laboratory assessment abnormalities(Up to Day 17 of Period 4 (Each period is 17 days))
- Number of participants with 12-lead ECG abnormalitie(Up to Day 17 of Period 4 (Each period is 17 days))
- Number of participants with physical examination abnormalities(Up to Day 18 of Period 4 (Each period is 17 days))