The efficacy and safety of donepezil in patients with Alzheimer'sdisease: Results of a US multicentre, randomized, double-blind,placebo-controlled trial
S.L. Rogers
Bok Engelsk 1996
| Utgitt | 1996
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| Omfang | Side 293- 303
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| Opplysninger | This study evaluated the efficacy and safety of donepezil in patientswith mild to moderately severe Alzheimer's disease, and examined therelationships between plasma donepezil concentration, red blood cellacetylcholinesterase (AChE) activity and clinical response. The trialwas of a multicenter, double-blind, parallel-group design andpatients were randomised to once-daily treatment with eitherdonepezil (1, 3 or 5 mg) or placebo. The 12-week double-blind phasewas followed by a 2-week single-blind placebo washout. 161 patients(55-85 years of age) entered the study and 141 completed treatment.Patients treated with donepezil showed dose-related improvements inthe Alzheimer's Disease Assessment Scale - cognitive subscale score(ADAS-cog) and in MMSE scores. The improvements in ADAS-cog werestatistically significantly greater with donepezil 5 mg/day than withplacebo. There was a 50% reduction in the percentage of patientsshowing clinical decline with donepezil at 5 mg/day (11%) relative toplacebo (20%). In addition, a statistically significant correlationbetween plasma concentrations of donepezil and AChE inhibition wasdemonstrated. A plateau of inhibition (76-84%) was reached at plasmadonepezil concentrations > 50 ng/ml. The correlation between plasmadrug concentrations and ADAS-cog (p = 0.014), MMSE (p = 0.023) andpatient quality of life scores, assessed by the patient (p = 0.037)were also statistically significant, as was the correlation betweenAChE inhibition and change in ADAS-cog (p = 0.008). The incidence oftreatment-emergent adverse events with all three dosages of donepezil(64-68%) was comparable to that observed with placebo (65%).Donepezil had no clinically significant effect on vital signs,haematology or clinical biochemistry tests. Importantly, donepezilwas not associated with any hepatotoxicity, as observed with acridine-based cholinesterase inhibitors.
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