A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Alzheimer's disease when administered for 29 days in a cross-over design
详细描述
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women of non-childbearing potential and men, aged 55-85 years
- •AD diagnosis based on the 2011 National Institute on Aging-Alzheimer's Association Guidelines
- •Supportive evidence for diagnosis of AD based upon positive CSF Aβ42 test, or documented history of positive amyloid-specific PET scan
- •Screening MMSE score of 16-26 points
- •Screening CDR Global Score of 0.5-1.0
- •Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits that require input for scale completion, assists the participant with compliance for at-home study treatment administration, and signs the necessary consent form (note: the caregiver is not required to stay in the unit)
- •Approved AD treatments (acetylcholinesterase inhibitors ± memantine) and other prescription medications must be stable for ≥1 month prior to screening and anticipated to be stable over the duration of the study
排除标准
- •Clinical history within 2 years of the screening visit or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
- •Magnetic resonance imaging (MRI) at screening (or within 1 year of screening visit) consistent with any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
研究组 & 干预措施
DNL747 First, Placebo Second
Subjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
干预措施: DNL747 (Drug)
DNL747 First, Placebo Second
Subjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
干预措施: Placebo (Drug)
Placebo First, DNL747 Second
Subjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
干预措施: DNL747 (Drug)
Placebo First, DNL747 Second
Subjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Randomization - Day 86
Number of Subjects with clinically significant neurological examination abnormalities
时间窗: Randomization - Day 86
Number of Subjects with laboratory test abnormalities
时间窗: Randomization - Day 86
次要结局
- Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747(Randomization - Day 86)
- Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747(Randomization - Day 86)
- Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747(Randomization - Day 86)
- Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747(Randomization - Day 86)
- Pharmacokinetic measure of CSF concentrations of DNL747(Randomization - Day 86)
- Pharmacodynamic measure of pS166 in PBMCs(Randomization - Day 86)