A Phase I, Randomized, Double-Blind, Placebo-Controlled, Two-Part, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 in Plasma and Cerebrospinal Fluid in Healthy Male and Non-Fertile Female Elderly Volunteers and in Mild-to-Moderate Alzheimer Disease Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Adverse event monitoring
研究概览
简要总结
This is a two-part multiple dose study in healthy male and female (of non-child bearing potential) elderly volunteers, and in Alzheimer's disease patients, to assess the safety, effects on the body, and blood, CSF, and urine drug levels of AZD3293. AZD3293 is being developed for the treatment of Alzheimer's Disease
详细描述
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Two-Part, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Effect on Biomarkers of AZD3293 in Plasma and Cerebrospinal Fluid in Healthy Male and Non-Fertile Female Elderly Volunteers and in Mild-to-Moderate Alzheimer Disease Patients
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1: Healthy elderly male and female (of non-childbearing potential) subjects.
- •Part 2: Male and non-fertile female AD patients.
- •Body mass index (BMI) between 19 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg.
- •Part 2: Clinical diagnosis of probable AD according to the NINCDS-ADRDA criteria.
- •Part 2: Manifestation of AD symptoms at least 6 months before randomization.
排除标准
- •Part 1: History or presence of psychiatric disease/condition, GI, renal, hepatic, cardiovascular, psychiatric, or retinal diseases or disorders.
- •Part 2: Significant disease affecting the CNS other than Alzheimer's disease, including but not limited to other dementias, other significant neurological or major psychiatric disease.
- •History of use of antipsychotic drugs , or chronic use of antidepressant or anxiolytic drugs.
- •Frequent use (more than 2 days per week during the last 12 weeks) of tobacco or other nicotine products.
- •History of neurological disease, including seizures, recent memory impairment, or clinically significant head injury.
研究组 & 干预措施
AZD3293
Part 1: Up to 6 sequential cohorts of healthy elderly subjects are planned, with multiple ascending doses, starting with 5 mg (subject to confirmation by the Safety Review Committee) Part 2: Up to 16 mild-to-moderate AD patients administered one to up to 3 dosage levels of AZD3293
干预措施: AZD3293 (Drug)
Placebo
Part 1: Placebo given (2 subjects in each cohort) Part 2: Placebo given (up to 4 subjects)
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse event monitoring
时间窗: From Baseline up to 20 days
Assessment of vital signs (blood pressure, pulse and body temperature) and physical exams
时间窗: From Baseline up to 20 days
Clinical laboratory tests (chemistry, hematology, urinalysis, renal safety)
时间窗: From Baseline up to 20 days
Assessment of 12-lead digital electrocardiograms to measure rhythm, rate, morphology, QT/QTc interval
时间窗: Fron Baseline up to 20 days
Assessment of telemetry, as reported by Investigator Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: From Baseline up to 20 days
Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
次要结局
- Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD)(Up to 17 days)
- Investigation of the effect of AZD3293 on plasma and cerebrospinal fluid (CSF) biomarkers relevant for Alzheimer Disease (AD) in mild-moderate AD patients in comparison to elderly healthy volunteers(Up to 17 days)
- Investigation of the multiple dose Pharmacokinetics for AZD3293 and its metabolite AZ13569724, including dose proportionality for AZD3293 following oral administration(Up 17 days)
- Investigation of the Pharmacokinetics/Pharmacodynamics relationship of the effect of AZD3293 on biomarkers relevant for Alzheimer Disease (AD) in plasma(Up to 17 days)