Safety, Tolerability, Pharmacokinetics, and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- To measure the concentration of Amyloid Beta in cerebral spinal fluid
研究概览
简要总结
This study is being conducted to determine the safety, tolerability, pharmacokinetics, and effects of EVP-0962 on cerebral spinal fluid Amyloid concentrations in healthy subjects and in subjects with mild cognitive impairment or early Alzheimer's disease.
详细描述
This is a randomized, double-blind, sequential escalating repeat daily dose study conducted in two parts. The first part is being conducted in healthy subjects and will evaluate safety, tolerability, and pharmacokinetics and pharmacodynamics of escalating EVP-0962 doses (10, 50 100 and 200 mg) or matching placebo following once-daily administration for 14 days. The second part will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics of EVP-0962 following once-daily administration for 14 days in patients with mild cognitive impairment or early Alzheimer's disease at the dose level selected based on the available safety, pharmacokinetics and pharmacodynamics observations in the first part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1: Male and female subjects between the ages of 45 to 65 (inclusive) in good health with a BMI of 18-32 kg/m2 and negative urine drug screen of abuse test.
- •Part 2: Male and female subjects between the ages of 45 to 85 (inclusive), MRI/CT scans compatible with diagnosis of MCI or early AD, meets the classification of MCI due to AD as defined by the National Institute on Aging-Alzheimer's Association, and a BMI of 18-32 kg/m2(inclusive). Subjects must meet the following Cognitive criteria: Subject Memory Complaint, cognitive impairment in one or more areas, CDR-SB score less than or equal 1.0, MMSE greater than 24, and no impairment in social or occupational functioning.
排除标准
- •History of seizure disorder, symptomatic orthostatic hypotension, QTc values greater than 450 ms, positive drug screening tests
- •Pregnancy, nursing, (or if fertile female) not willing to utilize birth control measures during study
- •C-SSRS suicidal ideation score of 4 or 5
- •Unwilling to abstain from vigorous exercise
- •Concurrent disease other than MCI or early AD that is attributing to patient's cognitive impairment.
- •Lumbar spine X-rays show anatomic contraindications to lumbar puncture
- •History of spinal surgery or chronic low back pain
- •History of migraine headaches
研究组 & 干预措施
Arm 1
10 mg EVP-0962 Orally administered once daily for 14 days
干预措施: EVP-0962 (Drug)
Arm 2
50 mg EVP-0962 Orally administered once daily for 14 days
干预措施: EVP-0962 (Drug)
Arm 3
100 mg EVP-0962 Orally administered once daily for 14 days
干预措施: EVP-0962 (Drug)
Arm 4
200 mg EVP-0962 Orally administered once daily for 14 days
干预措施: EVP-0962 (Drug)
Arm 5
Placebo orally administered for 14 days
干预措施: Placebo (Drug)
结局指标
主要结局
To measure the concentration of Amyloid Beta in cerebral spinal fluid
时间窗: 0-36 hours post dose
To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects
时间窗: 0-36 hours post dose
The number of adverse experiences reported by subjects and/or observed by investigator and repeated clinical evaluations of physical examinations, vital signs, 12-lead ECG (electrocardiogram), and lab tests (hematology, chemistry, urinalysis)
时间窗: Screening (Day-45 to Day -1) through Day 23 (end of study visit)
次要结局
- To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma(0-36 hours post dose)
- To measure the rate of synthesis of Amyloid Beta and steady-state levels in the cerebral spinal fluid in MCI or early Alzheimer's disease patients(0-36 hours post dose)