16w Interventional Study on Titration and Dose/Efficacy Assessment of Exelon in Chinese Alzheimer's Disease Patients

Study Overview
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Brief Summary
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To investigate the efficacy of Exelon capsule at maximal tolerated dose in mild to moderate Chinese AD patients via dosage titration from 3mg/d to 12mg/d in a 16 weeks duration

Official Title
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16 Weeks Interventional Study on Titration and Dose/Efficacy Assessment of Exelon (Rivastigmine) in Chinese Alzheimer's Disease Patients (INSTINCT)

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: ENA713


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Have a diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria and have a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria MMSE score of ≥ 10 and ≤ 26 The treatment naïve patient and the one who have stopped the donepezil, galantamine, huperzine A, or memantine at least 2 weeks Be in stable medical condition Have signed off informed consent form by patients or his/her legal guardian Key Exclusion Criteria: Severe AD Patients with a history of cerebrovascular disease, Active or uncontrolled epilepsy, Active hypothyroidism, asthma, CNS infection, other Neurodegenerative disorders, an advanced, severe, progressive, or unstable medical condition Attending other clinical trials or taking other clinical trial drugs A score of > 4 on the Modified Hachinski Ischemic Scale (MHIS); Patients who is using any AChEI or memantine

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENA713<br>Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks. | Drug: ENA713<br>* The following strengths of Rivastigmine capsules were provided: Rivastigmine capsule strengths: 1.5mg, 3mg, 4.5mg. The 6mg dose was administered as one 1.5mg capsule and one 4.5mg capsule, and when necessary, the 3mg dose could also be administered as two 1.5mg capsules. Rivastigmine was administered from 3mg/d at baseline. Then dose escalation was made in 3mg/d increments, at a minimun of 4 weeks between dose increases to a maximum dose of 12mg/d or the individual's best tolerated dose.<br>* Other names: Rivastigmine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) | The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) was used to measure change in cognitive function. Alzheimer's disease assessment scale (ADAS) is a scale to measure specific cognitive and behavior disorders in Alzheimer disease (AD) patients. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) provides a total score range 0-70, and consists of 11 items with lower score indicating lighter impairment and higher total scores indicating more impairment. A negative change score indicates improvement from baseline. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | ADCS-ADL is a scale based on caregiver's assessment of patient's activities of daily life. It is used in clinical studies on dementia & consists of 23 items and is designed to assess patient's basic & instrumental activities of daily life, such as the abilities necessary for personal care, communicating & interacting with other people, maintaining a household, conducting hobbies & interests, & making judgments & decisions. Response to each item is obtained by interview with the caregiver. The basic activities of daily life domain includes mandatory options for best response, or yes or no questions with separate sub-questions. Higher score & more yes answers indicate better level of self-care of patient. Therefore the higher the total score is, the better the patient's functions. The total score is the sum of the scores of all the items & sub-questions,& ranges from 0 to 78. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated. | Baseline, Week 16 | 
| Change From Baseline in Mini-Mental State Examination (MMSE) | MMSE was used to determine patient's eligibility to participate, is an easy & practical screening test to identify cognitive disorders. Test consists of 2 parts: language (time orientation, registration & attention) & performance (recall, response to written/verbal commands, writing ability & reproduction of complex polygons); total score range: 0-30; higher score = better function. Positive change score = improvement from baseline. To meet eligibility criteria, patient's MMSE total score at screening had to be 10-26 (inclusive). Interpretation of MMSE by 4 methods: Single Cut0ff: <24=abnormal; Range: <21=Increased odds of dementia; >25=Decreased odds of dementia; Education: 21- abnormal for 8th grade education, <23=abnormal for high school education, <24=abnormal for college education; Severity: 24-30=no cognitive impairment, 18-23=mild cognitive impairment, 0-17=severe cognitive impairment. 2-sided 95% CI of difference in means between baseline & post-baseline values were calculated | Baseline, Week 16 | 
| Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Score | This scale assesses a larger scope of the behavior problems/disorders experienced in dementia patients, and identifies the frequency & severity of the behavior disorders, & allows rapid assessment using screening questions. 10 questions in behavior domain & 2 in autonomic nervous system domain were assessed by the investigator interviewing with the caregiver. The NPI-12 total score is the total score of the 12 items, among which the score for each domain is the product of frequency (range: 1-4 points) and severity (range: 1-3 points). The highest score for each domain is 12 points and all the domains have the same weight. Therefore the range of NPI-12 total score is 0-144 points. The NPI-10 total score is the total score of the first 10 items 0-120, which constitute the original form of this scale. A higher NPI total score indicates more severe behavior disorder. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated. | Baseline, Week 16 | 
| Change From Baseline in Caregiver Burden Inventory (CBI) Score | CBI, formulated by Novak and Guest in 1989, is a relatively complete and effective scale to measure caregiver burden that has been extensively adopted internationally. CBI has a total of 24 items in 5 domains, i.e., time dependency items (items 1-5), development items (items 6-10), physical health items (items 11-14), social relations items (items 15-18), and emotional heath items (items 19-24). Each item is scored on a 5-point scale based on the intensity of burden (0-4 points), so that the total score is 0-96, a higher score indicating heavier burden. It is a self-administered scale that takes about 10-15 minutes to complete. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, ENA713, Chinese patients, INSTINCT