Randomized, Double-blind, Placebo Controlled, Multi-center Registration Trial to Evaluate the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease Receiving Acetylcholinesterase Inhibitors and/or Memantine
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 880
- 主要终点
- Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-sb)
研究概览
简要总结
This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 18 months.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of probable Alzheimer Disease (AD) with documented evidence of progression of disease
- •Mini Mental State Examination (MMSE) score of 21-26, inclusive
- •Clinical Dementia Rating global score of 0.5 or 1
- •Rosen-Modified Hachinski Ischemia Score less than or equal to 4
- •Brain magnetic resonance imaging (MRI) consistent with the diagnosis of probable AD
- •Concurrent use of cholinesterase inhibitor or memantine with stable dose for at least 3 months prior to randomization
- •Caregiver willing to participate and be able to attend clinic visits with patient
- •Ability to ingest oral medications
排除标准
- •Significant neurological or psychiatric disease other than Alzheimer's disease
- •Participants with evidence or history of severe drug allergies (resulting in dyspnea or severe rash).
- •Any contraindications to MRI (e.g., clinically significant claustrophobia, non-removable ferromagnetic implants). Patients with contraindications to MRI may undergo computed tomography (CT) on approval by sponsor.
- •Any contraindications to the FDG-PET study (e.g. allergy to any component of the FDG dose) in the cohort undergoing a PET scan.
- •Previous exposure to investigational or non-investigational therapies for Alzheimer's disease within 6 months of screening
- •History of cancer within the last 5 years except adequately treated cervical carcinoma in-situ, cutaneous basal cell or squamous cell cancer, or non-progressive prostate cancer not requiring treatment
- •Women of childbearing potential
- •Uncontrolled blood pressure and/or blood pressure above 160/100
- •Prescription medical food intended for dietary management of the metabolic processes associated with Alzheimer's disease.
- •Diagnosis or history of cerebrovascular stroke, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage.
- •Patients with unstable, uncontrolled diabetes (HbA1c > 7.7%) and those requiring insulin.
研究组 & 干预措施
Azeliragon 5mg
Azeliragon (TTP488) 5mg orally once daily for 18 months
干预措施: Azeliragon (Drug)
Placebo
Placebo orally once daily for 18 months
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-sb)
时间窗: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)
The CDR scale is used as a global measure of dementia and is completed by a clinician in the setting of detailed knowledge of the individual patient collected from interviews with the patient and caregiver (Berg, 1988). The CDR describes 5 degrees of impairment in performance on each of 6 categories including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. CDR ratings are 0 for healthy individuals, 0.5 for questionable dementia and 1, 2 and 3 for mild, moderate and severe dementia as defined in the CDR scale. The scores for each category can also be summed and this is known as the sum of box score (CSR-SB). Sum of box scores range from 0 to 18 with higher scores indicating greater cognitive impairment.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score
时间窗: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)
The ADAS-cog is a structured scale (approximately 40 minutes to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis (Rosen, 1984). The ADAS-cog scoring range for the version used in this study is from 0 to 70, with higher scores indicating greater cognitive impairment.
次要结局
- Change From Baseline in Continuous Oral Word Association Task (COWAT)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))
- Change From Baseline in Category Fluency Test (CFT)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))
- Change From Baseline in Alzheimer's Disease Cooperative Study- Activities of Daily Living Inventory (ADCS-ADL)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))
- Change From Baseline in Magnetic Resonance Imaging (MRI) Brain Volumetric Measures(Baseline and 18 months)
- Change From Baseline in Mini-Mental State Examination (MMSE)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))
- Change From Baseline in the Normalized Mean Composite SUVR of the 5 Regions(Baseline to 18 months)
- Change From Baseline in Neuropsychiatric Inventory (NPI)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))
- Change From Baseline in Dementia Quality of Life (DEMQOL)(Baseline and 18 months (A-Study); baseline and 12 months (B-Study))