Study AZ3110865, a Study Comparing SB-742457 or Donepezil Versus Placebo 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
- 576
- 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 efficacy, safety and tolerability of SB-742457 versus placebo in subjects with mild-to-moderate Alzheimer's disease. SB-742457 is an experimental treatment which increases the levels of certain chemicals in the brain that are often decreased in patients with 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SB-742457 - 15mg
SB-742457 - 15mg
干预措施: SB-742457 (Drug)
Placebo
干预措施: Placebo (Drug)
SB-742457 - 35mg
SB-742457 - 35mg
干预措施: SB-742457 (Drug)
Donepezil
干预措施: Donepezil (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 assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Week 0. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.
Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24
时间窗: Week 24
The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse).
次要结局
- Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24(Baseline (Week 0) and Week 24)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in ADAS-Cog Total Score at Week 12(Baseline (Week 0) and Week 12)
- CIBIC+ Score at Week 12(Week 12)
- Change From Baseline in RBANS Total Score at Week 12(Baseline (Week 0) and Week 12)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24(Baseline (Week 0) and Week 24)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24(Baseline (Week 0) and Week 24)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24(Baseline (Week 0) and Week 24)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12(Baseline (Week 0) and Week 12)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12(Baseline (Week 0) and Week 12)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12(Week 12)
- Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24(Baseline (Week 0) and Weeks 12 and 24)
- Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in MMSE Total Score at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24(Baseline (Week 0) and Week 24)
- Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12(Week 12)
- Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT)(Upto Week 24)
- Number of Participants With Hematology Data of PCC ATOT(Upto Week 24)
- Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24(Baseline (Week 0) and Weeks 12 and 24)
- Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs)(Upto Week 24)
- Number of Participants With Chemistry Data of PCC ATOT(Upto Week 24)
- Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Hematology Parameter Hematocrit(Baseline (Week 0) and Week 24)
- Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24(Baseline (Week 0) and Week 24)
- Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24(Baseline (Week 0) and Week 24)
- Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist(Upto Week 24)
- Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss)(One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose)
- Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss)(One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose)
- Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24(Baseline (Week 0) and Week 24)
- Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss)(Weeks 4, 8,12,18 and Week 24)