A 24 Week, Prospective, Randomized, Parallel-group, Double-blind, Multi-center Study (ENA713DUS44) Comparing the Effects of Rivastigmine Patch 15 cm^2 vs. Rivastigmine Patch 5 cm^2 on ACTivities of Daily Living and CognitION in Patients With Severe Dementia of the Alzheimer's Type (ACTION) and a 24-week Open-label Extension to Study ENA713DUS44
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 716
- 试验地点
- 95
- 主要终点
- Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
研究概览
简要总结
The core study assessed the efficacy of a higher dose of rivastigmine 13.3 mg/24 h transdermally (15 cm^2 patch) compared to a lower dose of the rivastigmine 4.6 mg/24 h transdermally (5 cm^2 patch) in patients with Severe Dementia of the Alzheimer's Type in a 24-week study. The extension study obtained additional safety and efficacy data, as well as provided the higher dose rivastigmine patch to all patients who completed the core study for an additional 24 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Diagnosis of probable Alzheimer's disease (AD) according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
- •A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤
- •Be able to complete at least 1 item on the Severe Impairment Battery (SIB).
- •Residing with someone in the community or in regular contact with the primary caregiver.
- •Be ambulatory or ambulatory with aid.
排除标准
- •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.
- •Patients currently residing in a nursing home.
- •Any current medical or neurological condition other than AD that could explain the patient's dementia.
- •A current diagnosis of probable or possible vascular dementia.
- •A current diagnosis of severe or unstable cardiovascular disease.
- •A current diagnosis of bradycardia (< 50 beats per minute [bpm]), sick-sinus syndrome, or conduction defects.
- •Clinically significant urinary obstruction.
- •History of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis.
- •Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day.
- •A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds.
- •Taken any of the following substances (at the time of the Baseline Visit [Visit 2]).
- •Succinylcholine-type muscle relaxants during the previous 2 weeks.
- •Lithium during the previous 2 weeks.
- •An investigational drug during the previous 4 weeks.
- •A drug or treatment known to cause major organ system toxicity during the previous 4 weeks.
- •Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved treatments for Alzheimer's disease during the previous 2 weeks, with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1).
- •Centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks.
- •Selegiline unless taken at a stable dose during the previous 4 weeks.
- •Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.
- •Extension study
- •Inclusion Criteria:
- •Complete the double-blind phase (Week 24) of the core study.
- •Provide, if mentally competent, a separate written informed consent prior to participation in the extension study. In addition, the patient's caregiver, will provide written informed consent prior to the patient's participation in the open-label extension study. If the patient is not able to provide written informed consent, written informed consent must be obtained from the legally authorized representative on the patient's behalf.
- •Continue to reside with someone in the community or in regular contact with the primary caregiver; patients who reside in an assisted living facility are eligible to participate.
- •Continue to have a primary caregiver willing to accept responsibility for supervising treatment (eg, application and removal of the patch daily at approximately the same time of day), assessing the condition of the patient throughout the extension study.
- •Must be medically stable and tolerating the current dose of rivastigmine patch as determined by the investigator.
- •Exclusion Criteria:
- •Refer to the core study protocol for full details of the exclusion criteria.
- •Patients who discontinued the core study due to any reason are excluded.
- •No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
- •Other protocol-defined inclusion/exclusion criteria applied to the study.
研究组 & 干预措施
Rivastigmine 13.3 mg/24 h transdermal patch
In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.
干预措施: Rivastigmine 4.6 mg/24 h (5 cm^2) (Drug)
Rivastigmine 13.3 mg/24 h transdermal patch
In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.
干预措施: Rivastigmine 9.5 mg/24 h (10 cm^2) (Drug)
Rivastigmine 13.3 mg/24 h transdermal patch
In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.
干预措施: Rivastigmine 13.3 mg/24 h (15 cm^2) (Drug)
Rivastigmine 13.3 mg/24 h transdermal patch
In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.
干预措施: Placebo (Drug)
Rivastigmine 4.6 mg/24 h transdermal patch
In the core study, patients received rivastigmine 4.6 mg/24 h daily. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-24, patients received rivastigmine 4.6 mg/24 h and placebo. No patients received this treatment in the extension study.
干预措施: Rivastigmine 4.6 mg/24 h (5 cm^2) (Drug)
Rivastigmine 4.6 mg/24 h transdermal patch
In the core study, patients received rivastigmine 4.6 mg/24 h daily. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-24, patients received rivastigmine 4.6 mg/24 h and placebo. No patients received this treatment in the extension study.
干预措施: Placebo (Drug)
结局指标
主要结局
Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
时间窗: Baseline of the core study to Week 24 of the core study
The ADCS-ADL-SIV is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.
Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
时间窗: Baseline of the core study to Week 24 of the core study
The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.
次要结局
- Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24(Baseline of the core study to Week 24 of the core study)
- Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24(Baseline of the core study to Week 24 of the core study)
- Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24(Baseline of the core study to Week 24 of the extension study)
- Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24(Baseline of the core study to Week 24 of the extension study)
- Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24(Baseline of the core study to Week 24 of the extension study)