A 24-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Evaluation of the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Transdermal Patch in Patients With Probable Alzheimer's Disease (MMSE 10-20)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 859
- 试验地点
- 1
- 主要终点
- Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
研究概览
简要总结
The purpose of this study was to investigate the 5cm^2 and 10cm^2 doses of rivastigmine transdermal patch in terms of efficacy and safety in patients with probable Alzheimer's Disease (MMSE [Mini Mental State Examination] 10-20). A 52-week extension phase evaluated the safety and tolerability of long-term treatment by rivastigmine transdermal patch in patients with probable Alzheimer's Disease (AD).
详细描述
Patients were randomly assigned in a double-blind manner to one of the 3 treatment arms (placebo, rivastigmine 5 cm^2 and rivastigmine 10 cm^2) in a ratio of 1:1:1. During the Double-blind treatment phase, patients entered a 16-week Titration Period followed by an 8-week Maintenance Period. During the open-label extension phase, all patients started treatment with a 2.5 cm^2 patch and the dose was increased to 10 cm^2 over a 16-week titration period, followed by a maintenance period of 36 weeks.
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
- Triple (Participant, Care Provider, 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
- •A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria
- •A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria
- •An MMSE score of > or = 10 and < or = 20
排除标准
- •A current DSM-IV diagnosis of major depression
- •Taken rivastigmine in the past
- •A score of > 5 on the Modified Hachinski Ischemic Scale (MHIS) Other protocol-defined inclusion/exclusion criteria may apply
- •Other protocol-defined inclusion/exclusion criteria may apply
- •Extension Phase Eligibility Criteria
- •Inclusion Criteria:
- •Patients who have completed the Double-blind Treatment Phase on study medication
- •Exclusion Criteria
- •Patients who have any important protocol deviations until the completion of the Double-blind Treatment Phase
研究组 & 干预措施
Placebo
Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
干预措施: Placebo (Drug)
rivastigmine 5 cm^2
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks and thereafter daily rivastigmine 5 cm^2 patch. For patients who experienced intolerability, the dose was adjusted to rivastigmine 2.5 cm^2 daily. Patients then entered the 8-week maintenance period during which time they continued to receive the dose of rivastigmine they were taking at the end of the titration period.
干预措施: Rivastigmine transdermal patch (Drug)
Rivastigmine 10 cm^2
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks, rivastigmine 5 cm^2 patch for the next 4 weeks, rivastigmine 7.5 cm^2 patch for the next 4 weeks and then rivastigmine 10 cm^2 patch for the final 4 weeks. For patients who experienced intolerability, the dose was adjusted downward. Patients then entered the 8-week maintenance period during which time they continued to receive the dose of rivastigmine they were taking at the end of the titration period.
干预措施: Rivastigmine transdermal patch (Drug)
结局指标
主要结局
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
时间窗: Baseline and Week 24
The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline.
Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
时间窗: Baseline and Week 24
The overall clinical rating of change from baseline to week 24 measured by the 7-point CIBIC plus-J scale. The Clinician's Interview-Based Impression of Change plus Caregiver Input consists of 3 subscales: Disability Assessment of Dementia Scale, Behavioral Pathology in Alzheimer's Disease Rating Scale and Mental Function Impairment Scale, as well as the Clinician's Global Impression of Change (CGIC). Participants are scored according to the following: 1. Markedly improved 2. Moderately improved 3. Minimally improved 4. Unchanged 5. Minimally worse 6. Moderately worse 7. Markedly worse
次要结局
- Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)(Baseline and Week 24)
- Change From Baseline in Mini-Mental State Examination (MMSE)(Baseline and Week 24)
- Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)(Baseline and Week 24)
- Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)(Baseline and Week 24)
- Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)(Extension Phase Baseline and Week 52 of extension phase)
- Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE)(Extension Phase Baseline and Week 52 of extension phase)
- Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale(Extension Phase Baseline and Week 52 of extension phase)