Safety, Tolerability and Efficacy Study of Tricaprilin (AC-1202) Administered for Ninety Days in Subjects With Probable Alzheimer's Disease of Mild to Moderate Severity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 152
- 试验地点
- 14
- 主要终点
- Number of subjects with treatment related adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and effectiveness of tricaprilin administered once a day for ninety days in subjects with mild to moderate, probable Alzheimer's disease.
详细描述
Substantial scientific evidence has shown that defects in glucose metabolism occur in Alzheimer's disease. Attempts to compensate for the reduced cerebral metabolic rates in AD have met with some success. Treatment of AD patients with high doses of glucose and insulin will raise cognitive scores. However, this effect is slight, and high doses of insulin can have adverse consequences. Administration of ketone bodies or their metabolic precursors such as medium chain triglycerides (MCTs) presents an attractive alternative to glucose and insulin. In a preliminary study, tricaprilin, an MCT, demonstrated pharmacological activity and statistically significant efficacy in improving short-term memory and attention performance after a single dose.
Participants will be randomized to receive either tricaprilin or a matching placebo, administered once a day by mixing powder in a glass of liquid. The treatment period will last 90 days, followed by a 2-week washout period. Each patient will be seen 5 times: at screening, baseline, and post-baseline days 45, 90, and 104. The visits will include physical and/or neuropsychological examinations, electrocardiograms (ECGs) and laboratory tests.
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
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent Form signed by patient and caregiver
- •Diagnosis of probably Alzheimer's disease of mild to moderate severity
- •Age 50 or older
- •If female, 2 years postmenopausal or surgically sterile
- •Hearing, vision, and physical abilities adequate to perform assessments (corrective aids allowed)
- •Caregiver to attend all visits, perform assessments, and supervise administration of study medication
- •CT or MRI within 24 months prior to screening compatible with a diagnosis of probably Alzheimer's disease
- •Modified Hachinski Ischemia Scale score of 4 or less
- •ADAS-Cog score between 15 and 35 inclusive at screening
- •MMSE score between 14 and 24 inclusive at screening
- •Stable medical condition for 3 consecutive months immediately prior to baseline
- •No clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results during screening
排除标准
- •Any condition that would, in the opinion of the Principal Investigator, render the patient or the caregiver unsuitable for the study, or place them at substantial risk of adverse outcome
- •Unwillingness or inability of the patient and/or caregiver to fulfill the requirements of the study
- •Resident in a skilled nursing facility
- •Any significant neurological disease other than probable AD (e.g. Parkinson's disease, Huntington's disease, brain tumor, normal pressure hydrocephalus, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of stroke, or history of head injury requiring hospitalization)
- •An alternate cause for dementia other than AD as determined by a required CT or MRI scan within 24 months prior to screening
- •Current history of major psychiatric disorder
- •Major depression as determined by a Cornell Scale for Depression in Dementia
- •Clinically significant hypothyroidism
- •Clinically significant B12 deficiency
- •Unstable or clinically significant cardiovascular disease
- •Diabetes of any type
- •History of tertiary syphilis
- •Cancer within 3 years prior to baseline, with the exception of squamous and basal cell carcinoma
- •Vital sign abnormalities
- •Clinically significant renal disease or insufficiency
- •Clinically significant hepatic disease or insufficiency
- •Alcohol consumption greater than 2 oz of spirits per day or 14 oz per week (1 oz of spirits is equal to 6 oz of wine or 12 oz of beer)
- •Current history of alcohol abuse or other substance abuse within 24 months prior to baseline
- •Known HIV infection
- •Use of any investigational compound within 30 days prior to screening
- •Use of prohibited medications (contact site for details)
- •Prior or current use of medium-chain triglycerides (MCTs) for medical purposes
- •Known allergies to coconut oil
研究组 & 干预措施
Matching Placebo to AC-1202
Placebo formulation, once daily. Administered orally
干预措施: Placebo (Other)
AC-1202
Tricaprilin formulation, once daily. Administered orally
干预措施: Tricaprilin (Drug)
结局指标
主要结局
Number of subjects with treatment related adverse events
时间窗: 104 days
AE incidence rate per treatment group
次要结局
- Pharmacokinetics (PK) profile of tricaprilin(Baseline, Day 45, Day 90)
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)(90 days)
- Clinical Global Impression of Change(90 days)
- Mini-Mental State Exam (MMSE)(90 days)