A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease

Objective: To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMM SE] scores of 5 to 17; Functional Assessment Staging score less than or equ al to6 at baseline). Methods: Two-hundred ninety patients were randomized t o treatment in this 24-week, double-blind, placebo-controlled trial. Patien ts received either donepezil 5 mg/day for the first 28 days and 10 mg/day t hereafter as per the clinician's judgment (n = 144) or placebo (n = 146). T he primary outcome measure was the Clinician's Interview-Based Impression o f Change with caregiver input (CIBIC+). Results: Patients' mean age was 73. 6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE scores at baseli ne were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34 for the pla cebo group. Patients receiving donepezil showed benefits on the CIBIC+, com pared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary m easures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) show ed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated pati ents completed the trial. Adverse events (AE) were experienced by 83% of do nepezil- and 80% of placebo-treated patients, the majority of which were ra ted mild in severity; 8% of donepezil- and 6% of placebo-treated patients d iscontinued because of AE. Laboratory and vital sign abnormalities were sim ilar between the treatment groups. Conclusion: These data suggest that done pezil's benefits extend into more advanced stages of AD than those previous ly investigated, with very good tolerability.