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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
donepezil
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, donepezil

Eligibility Criteria

45 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

donepezil 15mg titration

donepezil 10mg & 23 mg alternating

no titration of donepezil

Arm Description

donepezil 15mg during the first 4 weeks before escalation to 23mg

alternating donepezil 10mg and 23mg during the first 4 weeks before escalation to 23mg

no titration and direct escalation to 23mg donepezil

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

blood WBC
if WBC count is below 4000/uL or above 10000/uL, abnormal
blood BUN
if BUN level is above 30 mg/dL, abnormal
blood Creatinine
if creatinine level is above 1.4 mg/dL, abnormal
blood sodium
if sodium level is below 135mmol/L or above 145mmol/L, abnormal
blood potassium
if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal
blood AST/ALT
if AST or ALT level is above 50 IU/L, abnormal
weight loss
if the weight is decreased over 5% of body weight at screening visit, then weight loss
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
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

Full Information

First Posted
September 10, 2015
Last Updated
August 6, 2018
Sponsor
Asan Medical Center
Collaborators
Dong-A University, Myongji Hospital, Seoul National University Bundang Hospital, Seoul St. Mary's Hospital, Chung-Ang University, Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02550665
Brief Title
Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23mg
Acronym
ODESA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 2014 (Actual)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Dong-A University, Myongji Hospital, Seoul National University Bundang Hospital, Seoul St. Mary's Hospital, Chung-Ang University, Eisai Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's disease, donepezil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
donepezil 15mg titration
Arm Type
Experimental
Arm Description
donepezil 15mg during the first 4 weeks before escalation to 23mg
Arm Title
donepezil 10mg & 23 mg alternating
Arm Type
Experimental
Arm Description
alternating donepezil 10mg and 23mg during the first 4 weeks before escalation to 23mg
Arm Title
no titration of donepezil
Arm Type
Active Comparator
Arm Description
no titration and direct escalation to 23mg donepezil
Intervention Type
Drug
Intervention Name(s)
donepezil
Other Intervention Name(s)
aricept
Intervention Description
using different titration method for the first 4 weeks, and after the 4 weeks, 23mg/day orally
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (safety and tolerability)
Description
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)
Time Frame
Change from baseline at 4 week
Secondary Outcome Measure Information:
Title
blood WBC
Description
if WBC count is below 4000/uL or above 10000/uL, abnormal
Time Frame
12 week
Title
blood BUN
Description
if BUN level is above 30 mg/dL, abnormal
Time Frame
12 week
Title
blood Creatinine
Description
if creatinine level is above 1.4 mg/dL, abnormal
Time Frame
12 week
Title
blood sodium
Description
if sodium level is below 135mmol/L or above 145mmol/L, abnormal
Time Frame
12 week
Title
blood potassium
Description
if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal
Time Frame
12 week
Title
blood AST/ALT
Description
if AST or ALT level is above 50 IU/L, abnormal
Time Frame
12 week
Title
weight loss
Description
if the weight is decreased over 5% of body weight at screening visit, then weight loss
Time Frame
4 week, 8 week, 12 week
Title
drug compliance (counting of residual drug)
Description
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
Time Frame
4 week, 8 week, 12 week
Title
heart rate on Electrocardiography (ECG)
Description
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
Time Frame
12 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
34518459
Citation
Hong YJ, Han HJ, Youn YC, Park KW, Yang DW, Kim S, Kim HJ, Kim HJ, Lee Y, Kwon M, Lee JH; ODESA study (Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23 mg). Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer's Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial. Dement Geriatr Cogn Disord. 2021;50(3):289-295. doi: 10.1159/000518470. Epub 2021 Sep 10.
Results Reference
derived
PubMed Identifier
31039806
Citation
Hong YJ, Han HJ, Youn YC, Park KW, Yang DW, Kim S, Kim HJ, Kim JE, Lee JH; ODESA study (Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23 mg). Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer's disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial. Alzheimers Res Ther. 2019 May 1;11(1):37. doi: 10.1186/s13195-019-0492-1.
Results Reference
derived

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

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