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

Alzheimer's Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02550665
• Other study ID #: JHongLee
• Status: Completed
• Phase: Phase 3
• Start date: December 2014
• Est. completion date: October 2016

Study information

• Verified date: August 2018
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: October 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• donepezil
using different titration method for the first 4 weeks, and after the 4 weeks, 23mg/day orally

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (7)

Lead Sponsor	Collaborator
Asan Medical Center	Chung-Ang University, Dong-A University, Eisai Inc., Myongji Hospital, Seoul National University Bundang Hospital, Seoul St. Mary's Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	blood WBC	if WBC count is below 4000/uL or above 10000/uL, abnormal	12 week
Secondary	blood BUN	if BUN level is above 30 mg/dL, abnormal	12 week
Secondary	blood Creatinine	if creatinine level is above 1.4 mg/dL, abnormal	12 week
Secondary	blood sodium	if sodium level is below 135mmol/L or above 145mmol/L, abnormal	12 week
Secondary	blood potassium	if potassium level is below 3.5mmol/L or above 5.1mmol/L, abnormal	12 week
Secondary	blood AST/ALT	if AST or ALT level is above 50 IU/L, abnormal	12 week
Secondary	weight loss	if the weight is decreased over 5% of body weight at screening visit, then weight loss	4 week, 8 week, 12 week
Secondary	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
Secondary	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