Study AZ3110866, a Fixed Dose Study of SB-742457 Versus Placebo When Added to Existing Donepezil Treatment in Subjects With Mild-to-moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 682
- 试验地点
- 1
- 主要终点
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
研究概览
简要总结
The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects and their caregivers must provide informed consent prior to study entry.
- •Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
- •Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.
- •Female subjects of child-bearing potential must agree to abstinence or an approved form of birth control.
- •Subjects must have adequate blood pressure and laboratory values.
排除标准
- •Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
- •Subjects with known hypersensitivity to sunlight or a history of seizures, previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.
研究组 & 干预措施
DONEPEZIL + SB-742457 15 MG
SB-742457 - 15mg added to existing donepezil treatment
干预措施: SB-742457 15mg (Drug)
DONEPEZIL + SB-742457 15 MG
SB-742457 - 15mg added to existing donepezil treatment
干预措施: donepezil 5-10mg (Drug)
DONEPEZIL + PLACEBO
Placebo added to existing donepezil
干预措施: Placebo (Drug)
DONEPEZIL + PLACEBO
Placebo added to existing donepezil
干预措施: donepezil 5-10mg (Drug)
DONEPEZIL + SB-742457 35 MG
SB-742457 - 35mg added to existing donepezil
干预措施: SB-742457 35mg (Drug)
DONEPEZIL + SB-742457 35 MG
SB-742457 - 35mg added to existing donepezil
干预措施: donepezil 5-10mg (Drug)
结局指标
主要结局
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
时间窗: Baseline(Week 0) and Week 24
ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.
Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
时间窗: Baseline(Week 0) and Week 24
The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
次要结局
- Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48(Baseline (Week 0) and Week 12, 24, 36 and 48)
- Number of Participants With Parameters of Clinical Concern - Hematology(Up to Week 48)
- Change From Baseline in RBANS Score at Week 12, 36 and 48(Baseline (Week 0) and Week 12, 36 and 48)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase(Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal))
- Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48(Baseline (Week 0) and Week 12, 36 and 48)
- Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)(Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48)
- Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in CDR-SB Score at Week 12, 36 and 48(Baseline (Week 0) and Week 12, 36, 48)
- Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48(Baseline (Week 0) and Week 24 and 48)
- Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)(Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48)
- Change From Baseline in RBANS Scale in Participants With APOE4 Gene(Baseline (Week 0) to Week 24 and Week 48)
- Number of Participants With Parameters of Clinical Concern - Clinical Chemistry(Up to Week 48)
- Exposure Estimates for Donepezil (Cavgss)(Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48)
- Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene(Baseline (Week 0) to Week 24 and Week 48)
- Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene(Baseline (Week 0) to Week 24 and Week 48)