P4‐305: Withdrawn

placebo-controlled trials of MEM IR (10 mg BID; 2 monotherapy; 1 of patients on stable donepezil) and 1 trial of MEM ER (28 mg QD; patients on stable ChEI regimen) in moderate to severe AD. Efficacy outcomes included cognition (SIB), function (ADCS-ADL19), behavior (NPI), and global status (CIBICPlus), and clinically meaningful events were defined as the median decline at Endpoint for placebo-only treated patients; the K-M method was used to compare median time to reach this point in the treatment groups and an unadjusted log-rank test was performed on the intent-to-treat population. Results:Meaningful events were defined as declines of 4 points on SIB, 3 points on ADCS-ADL19, NPI total score increase 0, and final score 5 for CIBIC-Plus. The median times-to-events (days) were: SIB (PBO-only: 85; PBO+ChEI: 176 [P<0.0001 vs PBO-only]; MEM-only: 188 [P1⁄40.0001 vs PBO-only]; MEM+ChEI: >196 [P<0.0001 vs PBO-only]; all-PBO groups: 168; all-MEM groups: 193 [P1⁄40.0037 vs all-PBO]), ADCSADL19 (PBO-only: 125; PBO+ChEI: 127 [P1⁄40.9854 vs PBOonly]; MEM-only: 172 [P1⁄40.0445 vs PBO-only]; MEM+ChEI: 168 [P1⁄40.2390 vs PBO-only]; all-PBO: 127; all-MEM: 168 [P1⁄40.0127 vs all-PBO]), NPI (PBO-only: 85; PBO+ChEI: 84 [P<0.0001 vs PBO-only]; MEM-only: 101 [P1⁄40.3518 vs PBO-only]; MEM+ChEI: 87 [P1⁄40.0333 vs PBO-only]; all-PBO: 85; all-MEM: 88 [P1⁄40.0027 vs all-PBO]), and CIBIC-Plus (PBO-only: 126; PBO+ChEI: 126 [P1⁄40.4567 vs PBO-only]; MEM-only: 168 [P1⁄40.1429 vs PBO-only]; MEM+ChEI: 168 [P1⁄40.4011 vs PBO-only]; all-PBO: 126; all-MEM: 168 [P1⁄40.0205 vs all-PBO]). Conclusions: Time-to-event analyses support the conclusion that memantine alone or in combination with a ChEI is efficacious in delaying cognitive, functional, and behavioral declines in patients with moderate to severe AD.