Efficacy and Safety of Sustained Release Donepezil High Dose versus Immediate Release Donepezil Standard Dose in Japanese Patients with Severe Alzheimer’s Disease: A Randomized, Double-Blind Trial

Article type: Research Article

Authors: Homma, Akira^{a; *} | Atarashi, Hirotsugu^b | Kubota, Naoki^c | Nakai, Kenya^c | Takase, Takao^c

Affiliations: [a] Tokyo Dementia Care Research and Training Center, Tokyo, Japan | [b] Nippon Medical School Tama-Nagayama Hospital, Nippon Medical School, Tokyo, Japan | [c] Eisai Co., Ltd., Tokyo, Japan

Correspondence: [*] Correspondence to: Akira Homma, MD, Tokyo Dementia Care Research and Training Center, 1-12-1 Takaido-nishi, Suginami-ku, Tokyo 168-0071, Japan. Tel.: +81 3 3334 2173; Fax: +81 3 3334 2718; E-mail: [email protected].

Abstract: Background: Donepezil is an established treatment for mild, moderate, and severe Alzheimer’s disease (AD). An international study demonstrated superior efficacy of sustained release (SR) 23 mg/day donepezil over immediate release (IR) 10 mg/day donepezil for cognitive function, but not global function in moderate-to-severe AD. Objective: To demonstrate the superiority of SR 23 mg/day donepezil over IR 10 mg/day donepezil in Japanese patients with severe AD (SAD). Methods: In this multicenter, randomized, double-blind, parallel-group study, Japanese outpatients with SAD were randomly assigned to continue IR 10 mg/day or switch to SR 23 mg/day for 24 weeks. Endpoints included the Severe Impairment Battery (SIB), Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus), and safety. Results: Overall, 166 and 185 patients were randomized to receive IR 10 mg/day and SR 23 mg/day, respectively. SR 23 mg/day was not statistically superior to IR 10 mg/day by SIB (least squares mean difference [LSMD]: 0.0; 95% confidence interval [CI]: –1.7, 1.8; p = 0.981) or CIBIC-plus (LSMD: 0.2; 95% CI: 0.0, 0.4; p = 0.080). Common adverse events in the SR 23 mg group were decreased appetite, vomiting, diarrhea, and contusion. Safety findings were consistent with known safety profiles of donepezil. Conclusion: SR 23 mg/day donepezil was not superior to IR 10 mg/day donepezil regarding the efficacy endpoints for Japanese SAD. Considering that a 10 mg/day dose is approved for SAD in Japan, the present findings suggest that IR 10 mg/day donepezil is the optimal dosage for Japanese patients with SAD.

Keywords: Alzheimer’s disease, cholinesterase inhibitors, donepezil, double-blind study, Japan

DOI: 10.3233/JAD-151149

Journal: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 345-357, 2016