TY - JOUR
T1 - Open-label, multicenter, phase 3, extension study of the safety and efficacy of donepezil in patients with Alzheimer disease
AU - Doody, R. S.
AU - Geldmacher, D. S.
AU - Gordon, B.
AU - Perdomo, C. A.
AU - Pratt, R. D.
PY - 2001
Y1 - 2001
N2 - Background: Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function. Objective: To investigate the long-term benefits of donepezil treatment in patients with AD. Design: Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout). Interventions: All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged. Measures: Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes. Results: After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events. Conclusions: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.
AB - Background: Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function. Objective: To investigate the long-term benefits of donepezil treatment in patients with AD. Design: Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout). Interventions: All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged. Measures: Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes. Results: After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events. Conclusions: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.
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U2 - 10.1001/archneur.58.3.427
DO - 10.1001/archneur.58.3.427
M3 - Article
C2 - 11255446
AN - SCOPUS:0035103036
SN - 0003-9942
VL - 58
SP - 427
EP - 433
JO - Archives of neurology
JF - Archives of neurology
IS - 3
ER -