A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 In Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Incidence and severity 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 study carried out at a single site in 88 healthy male subjects and healthy female subjects of non childbearing potential to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.
详细描述
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Women of non-childbearing potential and men; aged 18-50 years, inclusive
- •BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg
排除标准
- •History of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
研究组 & 干预措施
Placebo
Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses
干预措施: Placebo (Drug)
DNL343
Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses
干预措施: DNL343 (Drug)
结局指标
主要结局
Incidence and severity 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: Time to maximum observed concentration (Tmax) of DNL343 in plasma
时间窗: Up to 20 days
PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma
时间窗: Up to 20 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma
时间窗: Up to 20 days
PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL343 in plasma
时间窗: Up to 20 days
PK parameter: The area under the concentration-time curve from zero to 12 or 24 hours for twice daily (BID) or once daily (QD) dosing, respectively (AUC0-τ) of DNL343 in plasma
时间窗: Up to 20 days
PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma
时间窗: Up to 20 days
次要结局
- PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)(Up to 20 days)
- The PD of DNL343 in blood as measured by percent reduction of integrated stress response (ISR) protein levels measured by enzyme-linked immunosorbent assay (ELISA)(Up to 20 days)
- The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR)(Up to 20 days)
- PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)(Up to 20 days)
- PK parameter: Estimation of renal clearance (CLR)(Up to 20 days)