Double-Blinded, Randomized, Placebo-Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986090 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Safety and tolerability of single dose measured by incidence, potential significance and clinical importance of AEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-986090 in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female (of not childbearing potential), ages 18-45 years, inclusive
- •BMI 18 to 32 kg/m2, inclusive
排除标准
- •Any significant acute or chronic medical illness
研究组 & 干预措施
Panel 1: BMS-986090 (0.5 mg) or Placebo
BMS-986090 0.5 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: BMS-986090 (Drug)
Panel 1: BMS-986090 (0.5 mg) or Placebo
BMS-986090 0.5 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 2: BMS-986090 (3 mg) or Placebo
BMS-986090 3 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: BMS-986090 (Drug)
Panel 2: BMS-986090 (3 mg) or Placebo
BMS-986090 3 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 3: BMS-986090 (10 mg) or Placebo
BMS-986090 10 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: BMS-986090 (Drug)
Panel 3: BMS-986090 (10 mg) or Placebo
BMS-986090 10 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 4: BMS-986090 (30 mg) or Placebo + KLH (1 mg)
BMS-986090 30 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And Keyhole limpet hemocyanin (KLH) 1 mg solution single intramuscular dose once
干预措施: BMS-986090 (Drug)
Panel 4: BMS-986090 (30 mg) or Placebo + KLH (1 mg)
BMS-986090 30 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And Keyhole limpet hemocyanin (KLH) 1 mg solution single intramuscular dose once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 4: BMS-986090 (30 mg) or Placebo + KLH (1 mg)
BMS-986090 30 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And Keyhole limpet hemocyanin (KLH) 1 mg solution single intramuscular dose once
干预措施: Keyhole limpet hemocyanin (Drug)
Panel 5: BMS-986090 (100 mg) or Placebo + KLH (1 mg)
BMS-986090 100 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: BMS-986090 (Drug)
Panel 5: BMS-986090 (100 mg) or Placebo + KLH (1 mg)
BMS-986090 100 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 5: BMS-986090 (100 mg) or Placebo + KLH (1 mg)
BMS-986090 100 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: Keyhole limpet hemocyanin (Drug)
Panel 6: BMS-986090 (100 mg) or Placebo
BMS-986090 100 mg solution single dose intravenously once
OR
Placebo matching with BMS-986090 0 mg solution single dose intravenously once
干预措施: BMS-986090 (Drug)
Panel 6: BMS-986090 (100 mg) or Placebo
BMS-986090 100 mg solution single dose intravenously once
OR
Placebo matching with BMS-986090 0 mg solution single dose intravenously once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 7: BMS-986090 (300 mg) or Placebo + KLH (1 mg)
BMS-986090 300 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: BMS-986090 (Drug)
Panel 7: BMS-986090 (300 mg) or Placebo + KLH (1 mg)
BMS-986090 300 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 7: BMS-986090 (300 mg) or Placebo + KLH (1 mg)
BMS-986090 300 mg solution single dose subcutaneously once
OR
Placebo matching with BMS-986090 0 mg solution single dose subcutaneously once
And KLH 1 mg solution single intramuscular dose once
干预措施: Keyhole limpet hemocyanin (Drug)
Panel 8: BMS-986090 (750 mg) or Placebo
BMS-986090 750 mg solution single dose intravenously once
OR
Placebo matching with BMS-986090 0 mg solution single dose intravenously once
干预措施: BMS-986090 (Drug)
Panel 8: BMS-986090 (750 mg) or Placebo
BMS-986090 750 mg solution single dose intravenously once
OR
Placebo matching with BMS-986090 0 mg solution single dose intravenously once
干预措施: Placebo matching with BMS-986090 (Drug)
Panel 9: BMS-986090 (150 mg) or Placebo
BMS-986090 150 mg solution subcutaneously once weekly for 4 weeks
OR
Placebo matching with BMS-986090 0 mg solution subcutaneously once weekly for 4 weeks
干预措施: BMS-986090 (Drug)
Panel 9: BMS-986090 (150 mg) or Placebo
BMS-986090 150 mg solution subcutaneously once weekly for 4 weeks
OR
Placebo matching with BMS-986090 0 mg solution subcutaneously once weekly for 4 weeks
干预措施: Placebo matching with BMS-986090 (Drug)
结局指标
主要结局
Safety and tolerability of single dose measured by incidence, potential significance and clinical importance of AEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests
时间窗: Up to Day 85 after single dose of BMS-986090
AE = Adverse event ECG = Electrocardiogram
Safety and tolerability of multiple dose measured by incidence, potential significance and clinical importance of AEs, as determined by medical review of AE reports, vital sign measurements, ECGs and results of physical examination and laboratory tests
时间窗: Up to Day 106 after multiple dose of BMS-986090
次要结局
- Maximum observed serum concentration (Cmax) of BMS-986090 single dose subcutaneous (SC) and intravenous (IV)(Days 1 -85)
- Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of single dose BMS-986090 SC and IV(Days 1 -85)
- Terminal serum half-life (T-HALF) of single dose BMS-986090 SC and IV(Days 1 -85)
- Total body clearance (CLT) of single dose BMS-986090 IV(Days 1 -85)
- Apparent volume of distribution at terminal phase (Vz/F) of single dose BMS-986090 SC(Days 1 -85)
- Time of maximum observed serum concentration (Tmax) of single dose BMS-986090 SC and IV(Days 1 -85)
- Area under the serum concentration-time curve in one dosing Interval [AUC(TAU)] of multiple dose BMS-986090 SC(Days 1 -106)
- Trough observed plasma concentration (Ctrough) of multiple dose BMS-986090 SC(Days 1 -106)
- Average concentration over a dosing interval (Css-avg) of multiple dose BMS-986090 SC(Days 1 -106)
- Degree of Fluctuation (DF) of multiple dose BMS-986090 SC(Days 1 -106)
- AUC accumulation index (AI_AUC); ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-986090 SC (multiple dose)(Days 1 -106)
- Cmax accumulation index (AI_Cmax); ratio of Cmax at steady state to Cmax after the first dose of BMS-986090 SC (multiple dose)(Days 1 -106)
- Apparent total body clearance (CLT/F) of multiple dose BMS-986090 SC(Days 1 -106)
- Anti-KLH immunoglobulin G (IgG) and IgM antibody levels of single dose BMS-986090 SC(Days 1 -85)
- Immunogenicity of BMS-986090 following single SC / IV infusion measured by frequency of subjects with positive anti-drug-antibody (ADA) assessment and frequency of subjects who develop positive ADA following a negative baseline(Days 1 -85)
- Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of single dose BMS-986090 SC and IV(Days 1 -85)
- Apparent total body clearance (CLT/F) of single dose BMS-986090 SC(Days 1 -85)
- Volume of distribution at terminal phase (Vz) of single dose BMS-986090 IV(Days 1 -85)
- Volume of distribution during steady state (Vss) of single dose BMS-986090 IV(Days 1 -85)
- Absolute bioavailability (F) of single dose BMS-986090 SC(Days 1 -85)
- Maximum observed serum concentration (Cmax) of multiple dose BMS-986090 SC(Days 1 -106)
- Time of maximum observed serum concentration (Tmax) of multiple dose BMS-986090 SC(Days 1 -106)
- Terminal serum half-life (T-HALF) of multiple dose BMS-986090 SC(Days 1 -106)
- Receptor occupancy (RO) of BMS-986090 following single SC or IV infusion(Days 1 -85)