Assessment of Safety, Tolerability, and Pharmacodynamic Effects of LY2886721 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations
研究概览
简要总结
The purpose of this Phase 1/Phase 2 study is to evaluate how the body handles the drug and the drug's effect on the body of participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD and who test positive for amyloid plaque.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets criteria for MCI due to AD or Mild AD
- •All participants will be required to undergo assessment via the Mini Mental State Examination (MMSE) scale at screening
- •Participants with MMSE scores of 20 to 26, inclusive, may be enrolled provided they meet the criteria for mild AD, as follows:
- •Participant meets the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
- •Clinical Dementia Rating Scale (CDR) score of 0.5 or 1
- •Positive scan for the presence of amyloid beta
- •Participants with MMSE of 27 to 30, inclusive, may be enrolled as participants with MCI due to AD provided they meet the following criteria:
- •Gradual and progressive change in memory function as reported by the participant or a caregiver during a period of more than 6 months
- •Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR): free recall ≤22 and total recall ≤46
- •Absence of dementia
- •Preservation of functional independence
- •Exclusion of other potential (vascular, traumatic, or medical) causes of cognitive decline, where possible
- •Positive scan for the presence of amyloid beta
- •Women must be postmenopausal
- •Men are required to use an approved barrier method of contraception if their partners are pregnant, or of childbearing potential and not using approved contraceptive methods
排除标准
- •Participant in another drug or device study
- •Have a history of frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's disease, Parkinson's disease, progressive supranuclear palsy (PSNP), or other movement disorder
- •Participants are not on a stable standard of care (acetylcholinesterase inhibitors, memantine) initiated less than 2 months prior to entry or have less than 4 weeks of stable therapy. Note: Stable standard of care is allowed.
- •Have had a serious infectious disease affecting the brain in the past 5 years
- •Have had a serious or repeat head injury
- •Have significant retinal impairment or disease
- •Have had a stroke or other circulation problems that are affecting current health
- •Have had a seizure
- •Have major depressive disorder and are not on a stable dose of medication. Participants who no longer meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV) criteria for major depression may be included
- •History of schizophrenia, bipolar disorder, or severe mental illness
- •History of alcohol or drug abuse
- •Have asthma, chronic obstructive pulmonary disease (COPD), or other breathing disease that is not controlled with medicine
- •Have human immunodeficiency virus (HIV) or syphilis
- •Are taking blood thinners
研究组 & 干预措施
Placebo
Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
干预措施: Placebo (Drug)
35 mg LY2886721
LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.
干预措施: LY2886721 (Drug)
70 mg LY2886721
LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.
干预措施: LY2886721 (Drug)
15 mg LY2886721
LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.
干预措施: LY2886721 (Drug)
结局指标
主要结局
Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations
时间窗: Baseline, 26 weeks
Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.
Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
时间窗: Baseline, 12 weeks
Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.
次要结局
- Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations(Baseline, 12 weeks, 26 weeks)
- Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE)(Baseline, 26 weeks)
- Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations(Baseline, 12 weeks, 26 weeks)