A First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of DNL201 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study conducted in three parts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index 18.5 to 35.0 kg/m², inclusive, and body weight of at least 50.0 kg at screening
- •In good health, determined by no clinically significant findings from medical history, physical examination, and vital sign measurements
- •Women of non-childbearing potential and men using contraceptive measures
排除标准
- •History of clinically significant hematological, renal, pancreatic, gastrointestinal, hepatic, cardiovascular, metabolic, endocrine, immunological, allergic disease, or other major disorders
- •History of asthma, chronic obstructive pulmonary disease, or emphysema
- •Clinically significant neurologic disorder
- •History of stomach or intestinal surgery or resection
- •History of malignancy
研究组 & 干预措施
DNL201
Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)
干预措施: DNL201 (Drug)
Placebo
Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
时间窗: Up to 20 days
PK parameter: Maximum observed concentration (Cmax) of DNL201 in plasma
时间窗: Up to 10 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL201 in plasma
时间窗: Up to 10 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL201 in plasma (single dosing only)
时间窗: Up to 10 days
PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL201 in plasma
时间窗: Up to 10 days
PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL201 in plasma (multiple dosing only)
时间窗: Up to 10 days
PK parameter: Apparent terminal elimination half-life (t1/2) of DNL201 in plasma
时间窗: Up to 10 days
次要结局
- Concentration of DNL201 in cerebrospinal fluid (CSF) (following selected single and multiple doses)(Up to 10 days)
- The pharmacodynamics of DNL201 in whole blood as measured by the percent change from baseline in pS935(Up to 10 days)