10, or I-squared > 50%. The U0126 chemical structure pooled analyses of clinical worsening included patients in the ITT set who had an assessment on all three efficacy scales. Safety was assessed in the all-patients-treated (APT) set, defined as all patients who were randomised to, and received at least one dose of, either placebo or memantine. Significance was calculated using Fisher’s exact test; P-values < 0.05 were considered statistically significant. Results Study population A total of 510 patients with moderate to severe AD (MOD-SEV subgroup; MMSE 5 to 19) (339 from MEM-MD-02, and 171 from MEM-MD-12; 264 receiving memantine added to donepezil, and 246 receiving placebo added to donepezil) were included in the ITT set. Of these, 367 patients (186 receiving memantine added to donepezil, and 181 receiving placebo added to donepezil) were part of the MOD subgroup (MMSE 10 to 19) (Figure ?(Figure1).
1). As expected, other than baseline MMSE score, there were no clinically relevant differences between treatment groups in terms of baseline demographics (Table ?(Table11). Table 1 Baseline patient demographics and MMSE scores (ITT set) Excluded patient population characteristics Table ?Table22 shows the baseline characteristics for the 327 patients (mean baseline MMSE 18.0) originally enrolled in MEM-MD-02 (65 of 404 patients) or MEM-MD-12 (262 of 433 patients) who did not meet inclusion criteria for this study and were excluded from the efficacy analysis.
Of the excluded patients who were part of the ITT set, 130 (all from MEM-MD-12; 90 receiving donepezil and 40 receiving a ChEI other than donepezil) met exclusion criteria for mild-stage AD (a baseline MMSE score of ?? 20); there were no significant differences in baseline MMSE between patients randomised to memantine (n = 63; MMSE = 21.1) or placebo (n = 67; MMSE = 21.0). A further 100 patients from the ITT set (all from MEM-MD-12) met baseline MMSE criteria for moderate AD (MMSE 10 to 19) but were excluded for receiving a ChEI other than donepezil; these patients also had no significant differences in baseline MMSE between those randomised to memantine (n = 47; MMSE 14.1) or placebo (n = 53; MMSE 15.0). Finally, 81 patients from the ITT set (56 from MEM-MD-02 and 25 from MEM-MD-12) were excluded for taking a dose of donepezil less Drug_discovery than 10 mg/day.
Table 2 Baseline characteristics of patients excluded nothing due to any reasona Efficacy in individual domains of AD (meta-analyses) After 24 weeks of treatment, patients in the MOD-SEV subgroup receiving memantine added to donepezil showed significantly better efficacy across all examined domains of cognition, function, and global status than patients treated with placebo added to donepezil. The overall standardised effect sizes for memantine versus placebo were: 0.36 (P < 0.0001) for cognition, 0.21 (P = 0.02) for function, and 0.23 (P = 0.