A Single-center, Open-label Positron Emission Tomography Study to Evaluate the Time-course of Displacement of [11C]UCB-J by Brivaracetam and Levetiracetam in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans
研究概览
简要总结
This study will estimate how fast two antiepileptic drugs (Levetiracetam and Brivaracetam) enter the human brain. Brain imaging will be used to measure how quickly the radioactive probe [11C]UCB-J exits the brain when Levetiracetam or Brivaracetam are given. This will be used to estimate how fast the antiepileptic drugs enter the brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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
- •Inclusion Criteria:
- •Subject is male or female and between 18 to 55 years of age (inclusive)
- •Subject is in good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history, physical and neurological examinations, vital signs, 12-lead Electrocardiography (ECG), and clinical laboratory tests
- •Female subjects of childbearing potential must have a negative pregnancy test; female subjects of childbearing potential have to confirm that, for 1 month prior to the first administration of the study medication and during the entire study until the Safety Follow-Up (SFU) Visit she will either use a highly effective contraceptive method (eg, oral contraception, intrauterine device, diaphragm with spermicide) or abstain from sexual activity that can cause pregnancy
排除标准
- •Exclusion Criteria:
- •History or presence of clinically significant respiratory, gastrointestinal, renal, hepatic, pancreatic, hematological, cardiovascular, musculoskeletal, genitourinary, immunological, or dermatological disorders, or any type of cancer
- •Subject has a history of a neurological diagnosis, including but not limited to stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, or any other neurological disorder that may influence the outcome or analysis of the scan results
- •History of donation of more than 450 mL of blood within 60 days prior to dosing in the Yale PET center or planned donation before 30 days has elapsed since intake of study drug
- •The subject has Magnetic Resonance Imaging -incompatible (MRI - incompatible) implants and other contraindications for MRI, such as a pacemaker, artificial joints, non-removable body piercings, etc.
- •Subjects who have received a diagnostic or therapeutic radiopharmaceutical less than 7 days prior to participation in this study
- •Participation in other recent research studies < 1 month or < 1 year for studies involving ionizing radiation that would cause the subject to exceed the yearly dose limits for healthy volunteers
研究组 & 干预措施
Levetiracetam
Cohort 1: Half of the subjects will receive LEV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration.
Cohort 2: Half of the subjects will receive LEV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of LEV (500 mg to 2500 mg) or BRV (50 mg to 200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session (Visit 4), 7 to 28 days after completion of their first session (Visit 3) to enter the BRV arm.
干预措施: [11C]UCB-J (Radiation)
Levetiracetam
Cohort 1: Half of the subjects will receive LEV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration.
Cohort 2: Half of the subjects will receive LEV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of LEV (500 mg to 2500 mg) or BRV (50 mg to 200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session (Visit 4), 7 to 28 days after completion of their first session (Visit 3) to enter the BRV arm.
干预措施: Levetiracetam (Drug)
Brivaracetam
Cohort 1:Half of the subjects will receive BRV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration.
Cohort 2:Half of the subjects will receive BRV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of BRV (50-200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session,7 to 28 days after completion of their first session to enter the LEV arm.
Cohort 3:void Cohort 4:Subjects will take oral BRV (25-100 mg bid) for 4 days and a single dose of BRV on Day 5. Pre-/post-block scans will be obtained at the first dose, one post-block scan after the last dose. Additional post-block scans may be obtained 8-10 and 28h or later after last dose; if last scan not needed, subject will return 7 to 28 days later for a post-block scan. Dose range for LEV in Cohort 4 will be 250 to <1500mg.
干预措施: [11C]UCB-J (Radiation)
Brivaracetam
Cohort 1:Half of the subjects will receive BRV as a 5 minute iv infusion during the second Positron Emission Tomography (PET) scan, 60 minutes after the start of [11C]UCB-J administration.
Cohort 2:Half of the subjects will receive BRV as a 5 minute iv infusion during the first PET scan, 60 minutes after the start of [11C]UCB-J administration. The dose of BRV (50-200 mg) will be decided based on the data obtained in Cohort 1. Subjects will return for a second PET imaging session,7 to 28 days after completion of their first session to enter the LEV arm.
Cohort 3:void Cohort 4:Subjects will take oral BRV (25-100 mg bid) for 4 days and a single dose of BRV on Day 5. Pre-/post-block scans will be obtained at the first dose, one post-block scan after the last dose. Additional post-block scans may be obtained 8-10 and 28h or later after last dose; if last scan not needed, subject will return 7 to 28 days later for a post-block scan. Dose range for LEV in Cohort 4 will be 250 to <1500mg.
干预措施: Brivaracetam (Drug)
结局指标
主要结局
Level of synaptic vesicle glycoprotein 2A (SV2A) receptor occupancy during the displacement scans
时间窗: Displacement scans (120 minutes)
The receptor occupancy will be determined using occupancy plots from the apparent volume of distribution, Vapp values.
Tracer-exit corrected halftimes of Brivaracetam or Levetiracetam entry
时间窗: Baseline (120 minutes) and Displacement scans (120 minutes)
Tracer-exit corrected halftimes of Brivaracetam or Levetiracetam entry will be estimated by subtracting the tracer clearance halftime from the displacement halftime.
Equilibrium tissue to plasma activity ratio (VT) of [11C]UCB-J
时间窗: Baseline (120 minutes) and Displacement scans (120 minutes)
The equilibrium tissue to plasma activity ratio (VT) will be used to quantify \[11C\]UCB-J binding in each brain region of interest before and after administration of Brivaracetam and Levetiracetam.
Tracer displacement halftimes
时间窗: Baseline (120 minutes) and Displacement scans (120 minutes)
Tracer displacement halftimes will be estimated from Displacement scans and Baseline scans on the average standardized uptake value (SUV) for all regions over time during 60-minute timeframe.
次要结局
未报告次要终点