Open-label, multicenter, phase 3, extension study of the safety and efficacy of donepezil in patients with Alzheimer disease

R. S. Doody, D. S. Geldmacher, Barry Gordon, C. A. Perdomo, R. D. Pratt

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)427-433
Number of pages7
JournalArchives of Neurology
Volume58
Issue number3
StatePublished - 2001
Externally publishedYes

Fingerprint

Alzheimer Disease
Safety
Placebos
Therapeutics
Controlled Clinical Trials
donepezil
Alzheimer's Disease
Efficacy
Digestive System
Cholinesterase Inhibitors
Double-Blind Method
Pharmaceutical Preparations
Cognition
Nervous System
Dementia
Placebo

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Open-label, multicenter, phase 3, extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. / Doody, R. S.; Geldmacher, D. S.; Gordon, Barry; Perdomo, C. A.; Pratt, R. D.

In: Archives of Neurology, Vol. 58, No. 3, 2001, p. 427-433.

Research output: Contribution to journalArticle

Doody, R. S. ; Geldmacher, D. S. ; Gordon, Barry ; Perdomo, C. A. ; Pratt, R. D. / Open-label, multicenter, phase 3, extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. In: Archives of Neurology. 2001 ; Vol. 58, No. 3. pp. 427-433.
@article{899ba590ec22423d9734052193a39a4e,
title = "Open-label, multicenter, phase 3, extension study of the safety and efficacy of donepezil in patients with Alzheimer disease",
abstract = "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.",
author = "Doody, {R. S.} and Geldmacher, {D. S.} and Barry Gordon and Perdomo, {C. A.} and Pratt, {R. D.}",
year = "2001",
language = "English (US)",
volume = "58",
pages = "427--433",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "3",

}

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, Barry

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.

UR - http://www.scopus.com/inward/record.url?scp=0035103036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035103036&partnerID=8YFLogxK

M3 - Article

C2 - 11255446

AN - SCOPUS:0035103036

VL - 58

SP - 427

EP - 433

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 3

ER -