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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: donepezil

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.

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Seoul St. Mary's Hospital; Seoul National University Bundang Hospital; Eisai Inc.; Dong-A University; Chung-Ang University; Myongji Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 10, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer's disease; donepezil
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: JHongLee