Objective: To compare the safety and efficacy of galantamine and donepezil in the treatment of patients with moderate-to-severe Alzheimer’s disease (AD) over 1 year.
Design: In a multicenter trial, patients diagnosed with moderate-to-severe AD (NINCDS-ADRDA criteria) were randomized to receive galantamine 16 mg/day (with the option to increase to 24 mg/day at Week 13) or donepezil 5 mg/day (with the option to increase to 10 mg/day at Week 4) for 52 weeks in a rater-blinded, randomized, comparative, parallel-group study.
Materials and methods: Efficacy was compared across multiple domains. The Bristol Activities of Daily Living Scale (BrADL) was used for function; assessment of cognition was performed using several scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The Cognitive Drug Research Assessment Scale (CDR) battery, which includes specific measures of attention, was performed at selected centers. Other outcome measures included the Screen for Caregiver Burden (SCGB), which measured the burden and resource utilization during the study.
Results: 182 patients were randomized to receive treatment (galantamine: n = 94; donepezil: n = 88) and were included in the intent-to-treat (ITT) analysis. Equivalent meaningful benefit was demonstrated for both drugs on BrADL. Significant advantages were found for galantamine on cognition at Weeks 13 and 26 (p £ 0.0001 for both time points vs baseline), as measured by MMSE. At Week 52, galantamine-treated patients had maintained MMSE scores similar to baseline (–0.52 ± 0.39, p = 0.18), but donepezil-treated patients had deteriorated significantly from baseline (–1.57 ± 0.42, p = 0.0003). When the moderate group (MMSE ³ 12) was analyzed at Week 52, galantamine was found to be significantly more effective than donepezil in maintaining cognition at baseline levels (p < 0.0001). Regarding ADAS-cog scores, there was no statistically significant difference in mean change from baseline to Week 52 between the treatment groups, but there was a statistical benefit in favor of galantamine in patients with baseline MMSE ³ 12 (p = 0.04). All 3 CDR attentional tasks demonstrated notable treatment responses to galantamine, being fast in onset and significant at 6 weeks. For all other outcome parameters, responses were equivalent for both groups. SCGB showed short-term significant improvement and long-term maintenance with galantamine versus donepezil. At study end, 79.2% of all patients had remained on therapy; 80.4% of patients initially randomized to receive galantamine remained on active therapy versus 78.0% of donepezil-treated patients. Of the 36 patients who experienced severe adverse reactions, 18 (18.6%) had received galantamine and 18 (19.8%) had received donepezil.
Conclusions: This study indicates that patients with moderate-to-severe AD, treated for 1 year, exhibit a better cognitive response with galantamine than with donepezil. The safety and tolerability profiles are similar for these agents.
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