A Randomized, Placebo-Controlled, Single and Multiple Ascending Subcutaneous Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986089 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Safety endpoints, including incidence of Adverse Event (AEs), serious AEs, AEs leading to discontinuation or death, as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, and physical examinations
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of single and multiple doses of BMS-986089 in healthy adult subjects.
详细描述
Primary Purpose - other: Protocol designed to assess the safety, tolerability, immunogenicity, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-986089 in healthy subjects
Enrollment: Single ascending dose panels: 48 subjects, Multiple ascending dose panels: 96
Minimum age: 18 years (Elderly MAD Panel 65 years of age) Maximum age: 55 years (Elderly MAD Panel 70 years of age)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
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
- •Healthy subjects as determined by no clinically significant deviation from normal medical history, physical examination, ECGs and clinical laboratory determinations
- •Men and women who are not of childbearing potential (ie, who are postmenopausal or Surgically sterile WOCBP) ages 21 to 55 years
- •Women must not be breastfeeding
- •Men who are sexually active with women of child bearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year
排除标准
- •Any significant acute or chronic medical illness Any major surgery within 6 weeks of study drug administration
- •Any condition that will clearly require medical or surgical treatment during the period of study participation
- •Any bone trauma or bone surgery within 3 months of study drug administration
- •Known or suspected autoimmune disorder
- •Donation of blood or plasma to a blood bank or in a clinical study (except at screening visit) within 6 weeks of study
研究组 & 干预措施
SAD Panel 1:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: Placebo matching with BMS-986089 (Drug)
SAD Panel 2:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: BMS-986089 (Drug)
SAD Panel 1:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: BMS-986089 (Drug)
SAD Panel 2:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: Placebo matching with BMS-986089 (Drug)
SAD Panel 3:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: BMS-986089 (Drug)
SAD Panel 3:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: Placebo matching with BMS-986089 (Drug)
SAD Panel 4:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: BMS-986089 (Drug)
SAD Panel 4:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: Placebo matching with BMS-986089 (Drug)
SAD Panel 5:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: BMS-986089 (Drug)
SAD Panel 5:BMS-986089/Placebo
BMS-986089 in a single subcutaneous administration
OR
Placebo matching with BMS-986089 in a single subcutaneous administration
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 1:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 1:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 2:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 2:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 3:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 3:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 4:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 4:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 5:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administration every 2 weeks
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 5:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administration every 2 weeks
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 6:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: BMS-986089 (Drug)
MAD Panel 6:BMS-986089/Placebo
BMS-986089 in multiple subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 in multiple subcutaneous administrations weekly
干预措施: Placebo matching with BMS-986089 (Drug)
MAD Panel 7:BMS-986089/Placebo
BMS-986089 a single subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 a single subcutaneous administration every 2 weeks
干预措施: BMS-986089 (Drug)
MAD Panel 7:BMS-986089/Placebo
BMS-986089 a single subcutaneous administrations weekly
OR
Placebo matching with BMS-986089 a single subcutaneous administration every 2 weeks
干预措施: Placebo matching with BMS-986089 (Drug)
结局指标
主要结局
Safety endpoints, including incidence of Adverse Event (AEs), serious AEs, AEs leading to discontinuation or death, as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, and physical examinations
时间窗: Multiple Ascending Dose (MAD) phase 148 days
次要结局
- Volume of distribution of terminal phase (if IV and if multi-exponential decline) (Vz/F) for SAD(SAD phase: Day1 to Day 91)
- Maximum observed serum concentration (Cmax) for SAD and MAD(SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120)
- Time of maximum observed serum concentration (Tmax) for SAD and MAD(SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120)
- Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) for SAD(SAD phase: Day1 to Day 91)
- Half life (T-Half) for SAD and MAD(SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120)
- Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) for MAD(MAD phase: Day 1 to Day 120)
- Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for SAD(SAD phase: Day1 to Day 91)
- Average concentration over a dosing interval (Css-Avg) for MAD(MAD phase: Day 1 to Day 120)
- Immunogenicity of single and multiple doses of BMS-986089 will be measured by testing for the presence of ADAs for SAD and MAD(30 days)
- Serum concentration 168 h post dose (C(168H)) for SAD and MAD(SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120)
- Apparent total body clearance (CLT/F) for SAD(SAD phase: Day1 to Day 91)
- Serum concentration 336 h post dose (C(336H)) for SAD and MAD(SAD phase: Day1 to Day 91, MAD phase: Day 1 to Day 120)
- Area under the concentration-time curve in one dosing interval (AUC(TAU)) for MAD(MAD phase: Day 1 to Day 120)
- C(336H) Accumulation Index; ratio of C(336H) at steady-state to C(336H) after the first dose (AI 336H) for MAD(MAD phase: Day 1 to Day 120)
- The pharmacodynamic effect of single and multiple doses of BMS-986089 on free myostatin, total myostatin (pre-dose only), and myostatin-drug complex will be assessed by measuring these biomarkers for SAD and MAD(30 days)
- Degree of Fluctuation or Fluctuation Index (DF) for MAD(MAD phase: Day 1 to Day 120)
- AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI AUC) for MAD(MAD phase: Day 1 to Day 120)
- Cmax Accumulation Index; ratio of Cmax at steady-state to Cmax after the first dose (AI Cmax) for MAD(MAD phase: Day 1 to Day 120)
- C(168H) Accumulation Index; ratio of C168H at steady-state to C168H after the first dose (AI C168H) for MAD(MAD phase: Day 1 to Day 120)