Clinical trial NCT02550665: Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23mg
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
donepezil
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Dong-A University
name: Myongji Hospital
name: Seoul National University Bundang Hospital
name: Seoul St. Mary's Hospital
name: Chung-Ang University
name: Eisai Inc.
First posted: 2015-09-15
Enrollment: 176
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Change from baseline at 4 week
Secondary outcomes:
measure: blood WBC
timeFrame: 12 week
measure: blood BUN
timeFrame: 12 week
measure: blood Creatinine
timeFrame: 12 week
measure: blood sodium
timeFrame: 12 week
measure: blood potassium
timeFrame: 12 week
measure: blood AST/ALT
timeFrame: 12 week
measure: weight loss
timeFrame: 4 week, 8 week, 12 week
measure: drug compliance (counting of residual drug)
timeFrame: 4 week, 8 week, 12 week
measure: heart rate on Electrocardiography (ECG)
timeFrame: 12 week
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
References:
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.
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.