A Randomized, Double-Blind, Placebo-Controlled and Delayed-Start Study of LY3314814 in Mild Alzheimer's Disease Dementia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 1,722
- 试验地点
- 257
- 主要终点
- Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy of the study drug known as lanabecestat in participants with mild Alzheimer's disease (AD) dementia.
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
- Triple (Participant, Care Provider, 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
- •Participant must meet the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (NIA-AA) criteria for probable AD dementia.
- •MMSE score of 20 to 26 inclusive at screening visit.
- •For a diagnosis of mild AD dementia, participant must have a CDR global score of 0.5 or 1, with the memory box score ≥0.5 at screening.
- •Evidence of amyloid pathology.
- •The participant must have a reliable study partner with whom he/she cohabits or has regular contact.
排除标准
- •Significant and/or current neurological disease affecting the central nervous system, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, repetitive head trauma, serious infection of the brain, Parkinson's disease, epilepsy, or cervicocranial vascular disease.
- •Participants with any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the participant's ability to complete the study. Participants with history of schizophrenia or other chronic psychosis are excluded.
- •Within 1 year before the screening visit or between screening and randomization, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptoms of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (such as, significant valvular disease, hypertrophic cardiomyopathy); or hospitalization for arrhythmia.
- •Congenital QT prolongation.
- •Intermittent second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.
- •A corrected QT (QTcF) interval measurement >470 milliseconds (men and women) at screening (as determined at the investigational site).
- •History of malignant cancer within the last 5 years.
- •History of vitiligo and/or current evidence of post-inflammatory hypopigmentation.
- •Calculated creatinine clearance <30 milliliters per minute (Cockcroft-Gault formula; Cockcroft and Gault 1976) at screening.
- •Currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
研究组 & 干预措施
Lanabecestat 20 milligrams (mg)
Participants received Lanabecestat 20 mg film-coated tablets orally once daily until week 156.
干预措施: Lanabecestat (Drug)
Lanabecestat 50 mg
Participants received Lanabecestat 50 mg film-coated tablets orally once daily until week 156.
干预措施: Lanabecestat (Drug)
Placebo/ Lanabecestat 20 mg
Placebo given orally once daily for 78 weeks and then 20 mg of lanabecestat given orally once daily until week 156.
干预措施: Lanabecestat (Drug)
Placebo/ Lanabecestat 20 mg
Placebo given orally once daily for 78 weeks and then 20 mg of lanabecestat given orally once daily until week 156.
干预措施: Placebo (Drug)
Placebo/ Lanabecestat 50 mg
Placebo given orally once daily for 78 weeks and then 50 mg of lanabecestat given orally once daily until week 156.
干预措施: Lanabecestat (Drug)
Placebo/ Lanabecestat 50 mg
Placebo given orally once daily for 78 weeks and then 50 mg of lanabecestat given orally once daily until week 156.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score
时间窗: Baseline, Week 78
ADAS-Cog13 (13-item version of ADAS Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.
次要结局
- Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score(Baseline, Week 78)
- Change From Baseline in Regional Cerebral Blood Flow (rCBF) Using Florbetapir Perfusion Scan(Baseline, Week 78)
- Change From Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)(Baseline, Week 78)
- Change From Baseline in Functional Activities Questionnaire (FAQ) Score(Baseline, Week 78)
- Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage(From Loss of 1 Global Stage through Week 78)
- Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score(Baseline, Week 78)
- Change From Baseline in Neuropsychiatric Inventory (NPI) Score(Baseline, Week 78)
- Change From Baseline in CSF Biomarker Total Tau(Baseline, Week 71)
- Change From Baseline on the Mini-Mental State Examination (MMSE)(Baseline, Week 78)
- Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40(Baseline, Week 71)
- Change From Baseline in CSF Biomarker Phosphorylated Tau(Baseline, Week 71)
- Change From Baseline in Whole Brain Volume(Baseline, Week 78)
- Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat(Predose, Week 4, 7, 19, 39, 45 and Week 71 post dose)
- Population PK: Central Volume of Distribution of Lanabecestat(Predose, Week 4, 7, 19, 39, 45 and week 71 post dose)
- Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42(Baseline, Week 71)
- Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan(Baseline, Week 78)