2a). OC analyses produced similar results for statistical significance and standardised effect sizes. There was no sign of heterogeneity in either LOCF or OC analyses. Figure 2 Meta-analyses of change from baseline to endpoint in individual domains of Alzheimer’s disease (LOCF analysis). aModerate to severe (AD) (MMSE 5 to 19 at baseline), receiving donepezil (10 kinase inhibitor 17-AAG mg/day). bModerate AD (MMSE 10 to 19 at baseline), receiving donepezil … Treatment with memantine added to donepezil was also associated with significant clinical benefits in the MOD subgroup. The overall standardised effect sizes for memantine versus placebo were: 0.28 (P = 0.008) for cognition, 0.21 (P = 0.04) for function, and 0.28 (P = 0.008) for global status (all LOCF; see Figure ?Figure2b).2b).

In OC analyses, memantine treatment was associated with statistical significance only for the global status measure, but similar overall standardised effect sizes were observed. There was no sign of heterogeneity in either LOCF or OC analyses. Efficacy in reducing the occurrence of marked clinical worsening In the MOD-SEV subgroup, 23/263 patients receiving memantine added to donepezil (8.7%) showed marked clinical worsening compared to 50/245 patients receiving placebo added to donepezil (20.4%), a significant difference of 11.7% (P = 0.0002; LOCF) (Figure ?(Figure3a).3a). The OC analysis produced a similar result (8.5% versus 18.9%; P = 0.003). Figure 3 Proportion of patients showing marked clinical worsening (ITT set, LOCF analysis). aModerate to severe AD (MMSE 5 to 19 at baseline), receiving donepezil (10 mg/day).

bModerate AD (MMSE 10 to 19 at baseline), receiving donepezil (10 mg/day). *P < ... In the MOD subgroup, 11/185 patients receiving memantine added to donepezil (5.9%) showed marked clinical worsening compared to 27/180 patients receiving placebo added to donepezil (15.0%), a significant difference of 9.1% (P = 0.006; LOCF) (Figure ?(Figure3b).3b). Again, the OC analysis produced a similar result (5.9% versus 12.6%; P = 0.047). Safety and tolerability - incidence of adverse events The incidence of AEs over 24 weeks was similar between the patients treated with memantine added to donepezil versus placebo added to donepezil (Table ?(Table3).3). In the MOD-SEV subgroup, the most common AEs with an incidence ?? 5% in patients treated with memantine added to donepezil were: dizziness, agitation, confusional state, diarrhoea, and nasopharyngitis (Table ?(Table3).

3). In the MOD subgroup, the most common AEs with an incidence ?? 5% in patients treated with memantine added to donepezil were: dizziness, diarrhoea, falls, Batimastat and urinary tract infection (Table ?(Table3).3). In both severity subgroups, the frequency of agitation Abiraterone FDA was statistically significantly lower in patients treated with memantine added to donepezil compared with patients treated with placebo added to donepezil (Table ?(Table3).3).