Single-Dose and Multiple-Dose, Dose-Escalation Study With LY2599666 to Evaluate the Safety, Pharmacokinetics, and Tolerability in Healthy Subjects and Patients With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild-to-Moderate Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY2599666 in different groups of people - those who are healthy, those who have mild cognitive impairment due to Alzheimer's Disease (AD), and those with mild-to-moderate AD. The study will measure how much LY2599666 gets into the bloodstream and how long it takes the body to get rid of it. It will also evaluate how LY2599666 affects the body. The study has three parts. Part A will last about 2 months. Parts B and C will each last about 23 weeks. Participants may only enroll in one 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Participants Part A:
- •Overtly healthy males or females as determined by medical history and physical examination
- •Have a body mass index (BMI) between 18.0 and 32.0 kilograms per meter squared (kg/m²), inclusive
- •Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) [Part B and C]:
- •Participants are at least 50 years old at screening
- •Present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD
- •Have a caregiver/study informant who provides a separate written informed consent to participate
- •Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator
- •Positive florbetapir scan
排除标准
- •All Participants
- •Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have known allergies to LY2599666, solanezumab, or any related compounds or components of the formulations, or have a history of significant atopy
- •Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
- •Have an abnormal blood pressure as determined by the investigator
- •Have significant allergies to humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisone
- •Require treatment with other monoclonal antibodies
- •Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) [Part B and C]
- •Have medical or surgical conditions in which lumbar puncture and or/catheter insertion is contraindicated
- •Have any contraindication for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI
- •Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) [Part C]
- •Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen post treatment
研究组 & 干预措施
Placebo (Part C)
Placebo given IV once weekly or once every 4 weeks for 12 weeks.
干预措施: Placebo IV (Drug)
Placebo (Part B)
Placebo given SC once weekly for 12 weeks (13 doses).
干预措施: Placebo SC (Drug)
Solanezumab (Part C)
Solanezumab given intravenously (IV) once weekly or once every 4 weeks for 12 weeks.
干预措施: Solanezumab (Drug)
LY2599666 (Part A)
LY2599666 given subcutaneously (SC) once.
干预措施: LY2599666 (Drug)
Placebo (Part A)
Placebo matching LY2599666 given SC once.
干预措施: Placebo SC (Drug)
LY2599666 (Part B)
LY2599666 given SC once weekly for 12 weeks (13 doses).
干预措施: LY2599666 (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline through 4 weeks (Part A) or 16 weeks (Part B )
Number of participants who experienced one or more treatment-emergent serious adverse events related to study treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
次要结局
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B))
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168 hours post-dose (Part B))
- Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A(Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A))
- Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B(Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B))