A Prospective, 5-Week, Open-Label, Randomized, Multi-Center, Parallel-Group Study With a 20-Week, Open-Label Extension Evaluating the Tolerability and Safety of Switching From Donepezil to an Initial Dose of 5 cm2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 262
- 试验地点
- 17
- 主要终点
- Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study
研究概览
简要总结
This study was designed to evaluate the safety and tolerability of switching from donepezil to an initial dose of 5cm^2 rivastigmine patch formulation in patients with probable Alzheimer's Disease (MMSE 10-24). The study included a 5-week, open-label, randomized period followed by a 20-week open-label extension period. Patients were randomized to either an immediate switch from donepezil to rivastigmine patch formulation or to a switch to rivastigmine patch formulation following a 7-day withdrawal period.
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
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be at least 50 years of age;
- •Have a diagnosis of probable Alzheimer's Disease;
- •Have an MMSE score of > or = 10 and < or = 24;
- •Must have a caregiver who is able to attend all study visits;
- •Have received continuous treatment with donepezil for at least 6 months prior to screening, and received a stable dose of 5 mg/day or 10 mg/day for at least the last 3 of these 6 months.
排除标准
- •Have an advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk;
- •Have a history of malignancy of any organ system, treated or untreated, within the past 5 years;
- •Have a history within the past year or current diagnosis of cerebrovascular disease;
- •Have a current diagnosis of severe or unstable cardiovascular disease; Have a history of myocardial infarction (MI) in the last six months;
- •Severe or unstable respiratory conditions (e.g., severe asthma , severe pulmonary (lung) disease);
- •Digestive problems related to peptic ulcer;
- •Urinary obstruction or current severe urinary tract infection;
- •Abnormal thyroid function tests;
- •Low folate or Vitamin B12;
- •Have a disability that may prevent the patient from completing all study requirements;
- •Have a current diagnosis of an active skin lesion/disorder that would prevent adhesion of a patch;
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Immediate Switch
Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
干预措施: Rivastigmine 5 cm^2 transdermal patch (Drug)
Immediate Switch
Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
干预措施: Rivastigmine 10 cm^2 transdermal patch (Drug)
Delayed Switch
Patients randomized to the delayed switch group were switched to 5 cm^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
干预措施: Rivastigmine 5 cm^2 transdermal patch (Drug)
Delayed Switch
Patients randomized to the delayed switch group were switched to 5 cm^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
干预措施: Rivastigmine 10 cm^2 transdermal patch (Drug)
结局指标
主要结局
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study
时间窗: Baseline through the end of the core phase of the study (Week 5)
The primary objective of the study was to evaluate the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD). The primary variable to assess tolerability of switching was the number of participants who discontinued from the study due to any reason during the core phase.
次要结局
- Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study(Baseline through the end of study (25 weeks))
- Number of Participants Who Discontinued From Study Due to Any Reason During Extension Phase(From week 5 through the end of extension phase (25 weeks))
- Mean Change From Baseline in the Clinical Global Impression of Change (CGIC) Score at Week 5 and Week 25(Baseline, Week 5 (end of the core phase) and Week 25 (end of the extension phase))
- Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 25 and at the End of Study(Baseline and Week 25 (end of the extension phase) and at the end of study)
- Mean Change From Baseline in Neuropsychiatric Inventory - 10 Item (NPI-10) Score at Week 25 and at the End of Study.(Baseline, Week 25 (end of the extension phase) and at End of Study)
- Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 25 and at the End of Study(Baseline, Week 25 (end of the extension phase) and at the end of Study)