An Open-Label Study To Evaluate The Safety and Tolerability Of A Novel LPA1 Receptor Positron Emission Tomography (PET) Ligand [11C]BMT-136088 And To Assess Receptor Occupancy In Human Lung Following Oral Administration Of BMS-986020 In Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Lung LPA1 percentage receptor occupancy of BMS-986020
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of a novel positron emission tomography (PET) tracer [11C]BMT-136088 in healthy adult subjects for measurement of availability of Lysophosphatidic Acid (LPA1) receptors in the human lung and to use this tracer to assess LPA1 receptor occupancy using [11C]BMT-136088 in the human lung following oral administration of Bristol Myers Squibb (BMS)-986020.
详细描述
End point Classification: Pharmacokinetics/Pharmacodynamics
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Body weight at least 50kg (110lbs), Body Mass Index (BMI) within 19 to 32 kg/m2, inclusive
- •Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests
- •Negative hepatitis panel and negative human immunodeficiency virus (HIV)antibody screens
排除标准
- •Any history or presence of clinically significant respiratory, Gastro Intestinal (GI), renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers
- •Any acute or chronic condition that, in the opinion of the investigator in consultation with the BMS Medical Monitor, could jeopardize the subject's safety, tolerability, or pharmacokinetics of the BMS-986020
- •Any major surgery within 4 weeks of study drug administration
- •Existence of a cold, upper respiratory tract infection, or fever within 5 days prior to check-in
- •Presence or history of any abnormality or illness that may affect absorption, distribution, metabolism or elimination of the study drug
- •Donation of blood or plasma (exclude the screening visit) within 2 months prior to check in through end of synthesis (EOS), inclusive
研究组 & 干预措施
Part 1: [11C]BMT-136088 (Safety Study)
Single PET SCAN with single bolus injection of [11C]BMT-136088
干预措施: [11C]BMT-136088 (Drug)
Part 2: [11C]BMT-136088 (Test/Retest study)
Single PET SCAN with Intravenous (IV) bolus plus infusion of [11C]BMT-136088 followed by a re-test PET scan (approximately 6 hours apart) with IV bolus plus infusion of [11C]BMT-136088
干预措施: [11C]BMT-136088 (Drug)
Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study)
BMS-986020 Tablets or Oral Solution of 4 dose levels from from the 6 dose levels of (50 mg, 150 mg, 300 mg, 600 mg, 1200 mg and 1500 mg) and 3 PET SCANS (Pre-Dose, Post-Dose1, Post-Dose2) with bolus plus infusion of [11C]BMT-136088
干预措施: BMS-986020 (Drug)
Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study)
BMS-986020 Tablets or Oral Solution of 4 dose levels from from the 6 dose levels of (50 mg, 150 mg, 300 mg, 600 mg, 1200 mg and 1500 mg) and 3 PET SCANS (Pre-Dose, Post-Dose1, Post-Dose2) with bolus plus infusion of [11C]BMT-136088
干预措施: [11C]BMT-136088 (Drug)
Part 4: [11C]BMT-136088 (Tissue Distribution study)
Single PET SCAN with [11C]BMT-136088 to evaluate additional tracer uptake sites in humans other than the lung, such as heart, kidney, liver, gallbladder, etc.
干预措施: [11C]BMT-136088 (Drug)
结局指标
主要结局
Lung LPA1 percentage receptor occupancy of BMS-986020
时间窗: Up to 2 days post BMS-986020 administration
Assessed by \[11C\]BMT-136088 tracer lung volume of distribution (VT) before and after single oral dose of BMS-986020.
Overall safety and tolerability of novel tracer [11C]BMT-136088
时间窗: Approximately up to 90 days
The following safety endpoints will be considered, the incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation from the study, and death as well as marked abnormalities in clinical laboratory tests, vital sign measurements, electrocardiograms (ECGs), and physical examinations occurring from screening up to study discharge.
次要结局
- Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986020(13 timepoints up to Day 3)
- Exposure-response relationship between lung LPA1 percentage receptor occupancy and BMS-986020 plasma concentration.(Up to 48 hr postdose (Approximately up to Day 3))
- Time of maximum observed concentration (Tmax) of BMS-986020(13 timepoints up to Day 3)
- Safety of single oral dose of BMS-986020 where [11C]BMT-136088 is administered to healthy subjects(Approximately up to 90 days)
- Maximum observed concentration (Cmax) of BMS-986020(13 timepoints up to Day 3)
- Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986020(13 timepoints up to Day 3)
- Half life (T-HALF) of BMS-986020(13 timepoints up to Day 3)