A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,496
- 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 48
研究概览
简要总结
Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG.
This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with the currently approved AD medication, Aricept (donepezil). RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects their response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.
详细描述
A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to donepezil on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-2)
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 90 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
Arm 1
Rosiglitazone Extended Release 2mg OD
干预措施: Rosiglitazone Extended Release 2mg (Drug)
Arm 1
Rosiglitazone Extended Release 2mg OD
干预措施: Donepezil (Other)
Arm 2
Rosiglitazone Extended Release 8mg OD
干预措施: Rosiglitazone Extended Release 8mg (Drug)
Arm 2
Rosiglitazone Extended Release 8mg OD
干预措施: Donepezil (Other)
Arm 3
Placebo
干预措施: Placebo (Other)
Arm 3
Placebo
干预措施: Donepezil (Other)
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 48
时间窗: Baseline (Week 0) and Week 48
ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in participants with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups. Least square mean is entered for adjusted mean.
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4
时间窗: Baseline (Week 0) and Week 48
CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups.
次要结局
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48(Baseline (Week 0) and Week 48)
- Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score(Baseline (Week 0), Week 8, 16, 24 and 48)
- Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score(Baseline (Week 0), Week 8, 16, 24 and 48)
- Change From Screening in Mini Mental State Examination (MMSE) Total Score(Screening (Week -4) and Week 48)
- Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD)(Baseline (Week 0), Week 12, 24, 36 and 48)
- Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48(Week 48 and 54)
- Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility(Baseline (Week 0), Week 12, 36 and 48)
- Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48(Baseline (Week 0), Week 8, 16, 24, 36 and 48)
- Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48(Baseline (Week 0), Week 12, 24, 36 and 48)
- Change in CDR-SB Total Score at Week 54 Compared to Week 48(Week 48 and 54)
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 54)
- Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP)(Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56)
- Mean Change From Baseline in Heart Rate(Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56)
- Change From Baseline in Hemoglobin Values(Baseline (Week 0), Week 4, 16, 36 and 48)
- Mean Change From Baseline in Weight(Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56)
- Change From Baseline in Hematocrit Values(Baseline (Week 0), Week 4, 8, 12, 16, 36 and 48)
- Mean Change From Baseline in Short Term Memory Assessment Score(Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56)
- Change From Baseline in HbA1c at Week 12, Week 24 and Week 36(Baseline (Week 0) and Week 12, 24 and 36)
- Number of Participants With Laboratory Potential Clinical Concern (PCC) Values(Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56)
- Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score(Baseline (Week 0), Week 12, 36 and 48)