Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23mg

Study Overview
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Brief Summary
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This study evaluates the side effects of dose escalation in the treatment of donepezil 23mg for patients with Alzheimer's disease. Investigators randomly divide participants into three groups according to the dose escalation method; no titration, 15mg of donepezil for a month before escalation to 23mg, and alternating of 10mg and 23mg for a month before escalation to 23mg.

Detailed Description
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High dose of donepezil is currently prescribed for patients with Alzheimer's disease who showed poor response in lower dose, however the side effect profiles according to dose titration method were not clarified yet. This study aims to confirm which titration method would show better safeties and tolerabilities in the high dose donepezil treatment. Investigators include patients with moderate to severe dementia who were diagnosed as probable Alzheimer's disease and treated with donepezil 10mg at least 3 months before the study. The study duration is for 12 weeks and the titration duration is the first 4 weeks of the study. Investigators evaluate the side effects profiles and vital signs at every 4 weeks and measure blood laboratory tests at screening and the last visit.

Official Title
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A Multicenter, Randomized, Open-label, Prospective Trial to Evaluate the Safety and Tolerability of Donepezil 23 mg With or Without Intermediate Dose Titration in Patients With Alzheimer's Disease Taking Donepezil Hydrochloride 10 mg

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: donepezil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria probable Alzheimer's disease dementia according to National Institute on Aging-Alzheimer's Association (NIAAA) criteria Mini-Mental State Examination (MMSE) score of 20 or less General Deterioration Scale (GDS) score of 4 or more / Clinical Dementia Rating (CDR) score of 2 or more stable dose of 10mg donepezil at least 3 months before screening caregiver who can come together at every visit and give informations about side effects profiles should exist patients and caregivers accepted the study Exclusion Criteria: patients receiving other concomitant acetylcholinesterase inhibitor uncontrolled psychiatric disorders drug overuse or alcohol abuse history within 5 years significant uncontrolled or active medical conditions uncontrolled epilepsy patients who cannot come at scheduled visits

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 90 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: donepezil 15mg titration<br>donepezil 15mg during the first 4 weeks before escalation to 23mg | Drug: donepezil<br>* using different titration method for the first 4 weeks, and after the 4 weeks, 23mg/day orally<br>* Other names: aricept;|
| Experimental: donepezil 10mg & 23 mg alternating<br>alternating donepezil 10mg and 23mg during the first 4 weeks before escalation to 23mg | Drug: donepezil<br>* using different titration method for the first 4 weeks, and after the 4 weeks, 23mg/day orally<br>* Other names: aricept;|
| Active Comparator: no titration of donepezil<br>no titration and direct escalation to 23mg donepezil | Drug: donepezil<br>* using different titration method for the first 4 weeks, and after the 4 weeks, 23mg/day orally<br>* Other names: aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (safety and tolerability) | adverse events (nausea, vomiting, diarrhea, anorexia, abdominal pain, headache and other unpredicted adverse events)are asked and assessed using 3 grade scale (mild, moderate, severe) | Change from baseline at 4 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood WBC | if WBC count is below 4000/uL or above 10000/uL, abnormal | 12 week | 
| blood BUN | if BUN level is above 30 mg/dL, abnormal | 12 week | 
| blood Creatinine | if creatinine level is above 1.4 mg/dL, abnormal | 12 week | 
| blood sodium | if sodium level is below 135mmol/L or above 145mmol/L, abnormal | 12 week | 
| blood potassium | if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal | 12 week | 
| blood AST/ALT | if AST or ALT level is above 50 IU/L, abnormal | 12 week | 
| weight loss | if the weight is decreased over 5% of body weight at screening visit, then weight loss | 4 week, 8 week, 12 week | 
| drug compliance (counting of residual drug) | if the (number of prescribed drugs - number of residual drugs)/ number of prescribed drugs is below 80%, then consider as low compliance, if compliance is between 80-100% then consider as good compliance | 4 week, 8 week, 12 week | 
| heart rate on Electrocardiography (ECG) | checking whether heart rate on ECG is normal because donepezil can cause bradycardia; if the heart rate is decreased below 50, then write down as bradycardia | 12 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, donepezil