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

Asan Medical Center

Status and phase: Completed; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: donepezil

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02550665

JHongLee

Details and patient eligibility

About

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.

Full 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.

Enrollment: 176 patients

Sex: All

Ages: 45 to 90 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

176 participants in 3 patient groups

donepezil 15mg titration

Experimental group

Description:

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

Treatment:

Drug: donepezil

donepezil 10mg & 23 mg alternating

Experimental group

Description:

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

Treatment:

Drug: donepezil

no titration of donepezil

Active Comparator group

Description:

no titration and direct escalation to 23mg donepezil

Treatment:

Drug: donepezil