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

This study is ongoing, but not recruiting participants.

Sponsor:

Collaborators:

Dong-A University

Myongji Hospital

Seoul National University Bundang Hospital

Seoul St. Mary's Hospital

Chung-Ang University

Eisai Inc.

Information provided by (Responsible Party):

Jae-Hong Lee, Asan Medical Center

ClinicalTrials.gov Identifier:

NCT02550665

First received: September 10, 2015

Last updated: July 15, 2016

Last verified: July 2016

History of Changes

Purpose

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.

Condition	Intervention	Phase
Alzheimer's Disease	Drug: donepezil	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Donepezil hydrochloride Donepezil

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by Jae-Hong Lee, Asan Medical Center:

Primary Outcome Measures:

Incidence of treatment-emergent adverse events (safety and tolerability) [ Time Frame: 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:

blood WBC [ Time Frame: 12 week ]
if WBC count is below 4000/uL or above 10000/uL, abnormal
blood BUN [ Time Frame: 12 week ]
if BUN level is above 30 mg/dL, abnormal
blood Creatinine [ Time Frame: 12 week ]
if creatinine level is above 1.4 mg/dL, abnormal
blood sodium [ Time Frame: 12 week ]
if sodium level is below 135mmol/L or above 145mmol/L, abnormal
blood potassium [ Time Frame: 12 week ]
if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal
blood AST/ALT [ Time Frame: 12 week ]
if AST or ALT level is above 50 IU/L, abnormal
weight loss [ Time Frame: 4 week, 8 week, 12 week ]
if the weight is decreased over 5% of body weight at screening visit, then weight loss
drug compliance (counting of residual drug) [ Time Frame: 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) [ Time Frame: 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


Enrollment:	176
Study Start Date:	December 2014
Estimated Study Completion Date:	October 2016
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: 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 Name: aricept

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.

Eligibility


Ages Eligible for Study:	45 Years to 90 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02550665

Locations


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

Sponsors and Collaborators

Asan Medical Center

Dong-A University

Myongji Hospital

Seoul National University Bundang Hospital

Seoul St. Mary's Hospital

Chung-Ang University

Eisai Inc.

More Information


Responsible Party:	Jae-Hong Lee, Principal investigator, Asan Medical Center
ClinicalTrials.gov Identifier:	NCT02550665 History of Changes
Other Study ID Numbers:	JHongLee
Study First Received:	September 10, 2015
Last Updated:	July 15, 2016

Keywords provided by Jae-Hong Lee, Asan Medical Center:


Alzheimer's disease donepezil

Additional relevant MeSH terms:


Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders	Donepezil Cholinesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Nootropic Agents

ClinicalTrials.gov processed this record on July 14, 2017

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