Table III.
Change in ADAS-cog and CDR-SB (Adjusted Models – ITT population
Visit / parameter | ADAS-Cog | CDR-SB | ||||
---|---|---|---|---|---|---|
Placebo BID | 100 mg BID | 150 mg BID | Placebo BID | 100 mg BID | 150 mg BID | |
(N = 341) | (N = 335) | (N = 329) | (N = 341) | (N = 335) | (N = 329) | |
Baseline/n | 331 | 325 | 318 | 336 | 327 | 320 |
Mean (SD) | 22.2 (8.3) | 22.1 (8.6) | 21.7 (8.3) | 5.8 (2.8) | 5.7 (2.6) | 5.7 (2.5) |
Week 13/n | 297 | 295 | 293 | 302 | 299 | 295 |
LS mean change | -1.6 | -1.2 | -1.5 | 0.2 | 0.4 | 0.2 |
95% CI | -3.2;-0.0 | -2.8-0.4 | -3.0-0.1 | -0.2-0.7 | -0.1-0.8 | -0.3-0.6 |
Difference (%) vs. placebo | 0.4 (-25.0) | 0.1 (-6.3) | 0.2 (100.0) | 0.0 (0.0) | ||
P-value | 0.302 | 0.761 | 0.314 | 0.656 | ||
Week 26/n | 294 | 277 | 277 | 296 | 281 | 276 |
LS mean change | -0.2 | -1.0 | -0.7 | 0.8 | 0.7 | 0.6 |
95% CI | -1.8-1.4 | -2.6-0.6 | -2.3-0.9 | 0.3-1.2 | 0.3-1.2 | 0.2-1.1 |
Difference (%) vs.placebo | -0.8 (400.0) | -0.5 (250.0) | -0.1 (-12.5) | -0.2 (-25.0) | ||
P-value | 0.065 | 0.223 | 0.703 | 0.276 | ||
Week 39/n | 265 | 264 | 264 | 268 | 266 | 265 |
LS mean change | 1.0 | 0.7 | 0.9 | 1.2 | 1.2 | 1.0 |
95% CI | -0.7-2.7 | -1.0-2.4 | -0.8-2.6 | 0.7-1.7 | 0.7-1.7 | 0.5-1.5 |
Difference (%) vs.placebo | -0.3 (-30.0) | -0.1 (-10.0) | -0.0 (0.0) | -0.2 (-16.7) | ||
P-value | 0.525 | 0.845 | 0.721 | 0.329 | ||
Week 52/n | 260 | 259 251 | 261 | 258 | 250 | |
LS mean change | 3.1 | 2.0 | 2.3 | 2.0 | 1.8 | 1.7 |
95% CI | 1.4-4.8 | 0.4-3.7 | 0.6-4.0 | 1.5-2.5 | 1.3-2.3 | 1.2-2.2 |
Difference (%) vs.placebo | -1.1 (-35.5) | -0.8 (-25.8) | -0.2 (-10.0) | -0.3 (-15.0) | ||
P-value | 0.090 | 0.193 | 0.335 | 0.136 | ||
Week 65/n | 246 | 243 | 236 | 247 | 244 | 237 |
LS mean change | 4.5 | 3.8 | 4.2 | 2.5 | 2.3 | 2.3 |
95% CI | 2.8-6.3 | 2.1-5.5 | 2.5-5.9 | 2.0-3.0 | 1.8-2.8 | 1.8-2.8 |
Difference (%) vs.placebo | -0.7 (-15.6) | -0.3 (-6.7) | -0.2 (-8.0) | -0.2 (-8.0) | ||
P-value | 0.217 | 0.535 | 0.280 | 0.378 | ||
Week 78/n | 248 | 242 | 229 | 245 | 243 | 233 |
LS mean change | 6.2 | 5.4 | 6.3 | 3.0 | 2.7 | 3.0 |
95% CI | 4.5-7.9 | 3.6-7.1 | 4.6-8.0 | 2.5-3.5 | 2.2-3.2 | 2.5;3.5 |
Difference (%) vs.placebo | -0.8 (-12.9) | 0.1 (1.6) | -0.3 (-10.0) | 0.0 (0.0) | ||
P-value | 0.174 | 0.873 | 0.232 | 0.915 |
Higher scores on ADAS-cog and CDR-SB indicate greater impairment and LS mean changes from Baseline > 0 indicate deterioration. The following covariates and covariate interactions were retained in the adjusted ANCOVA Models. ADAS-cog: Race, Type of ChEI Used, Age (quartiles), Disease Severity, Vitamin E dose, Antidepressant Use, Genotype, Visit X Disease Severity, Visit X Age (quartiles), and Visit X Memantine Dose. CDR-SB: Cardiovascular Disease, Type of ChEI Used, Disease Severity, Memantine Use, Years of Education (quartiles), Antidepressant Use, Genotype, Vitamin E Use, and Visit X Disease Severity