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

Phase 3
Completed
Conditions
Alzheimer's Disease
Interventions
Registration Number
NCT02550665
Lead Sponsor
Asan Medical Center
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
176
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
donepezil 15mg titrationdonepezildonepezil 15mg during the first 4 weeks before escalation to 23mg
donepezil 10mg & 23 mg alternatingdonepezilalternating donepezil 10mg and 23mg during the first 4 weeks before escalation to 23mg
no titration of donepezildonepezilno titration and direct escalation to 23mg donepezil
Primary Outcome Measures
NameTimeMethod
Incidence of treatment-emergent adverse events (safety and tolerability)Change from baseline at 4 week

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)

Secondary Outcome Measures
NameTimeMethod
blood WBC12 week

if WBC count is below 4000/uL or above 10000/uL, abnormal

blood Creatinine12 week

if creatinine level is above 1.4 mg/dL, abnormal

drug compliance (counting of residual drug)4 week, 8 week, 12 week

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

heart rate on Electrocardiography (ECG)12 week

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

blood sodium12 week

if sodium level is below 135mmol/L or above 145mmol/L, abnormal

blood potassium12 week

if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal

weight loss4 week, 8 week, 12 week

if the weight is decreased over 5% of body weight at screening visit, then weight loss

blood BUN12 week

if BUN level is above 30 mg/dL, abnormal

blood AST/ALT12 week

if AST or ALT level is above 50 IU/L, abnormal

Trial Locations

Locations (1)

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

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