Table 3. ADAS-cog and CDR changes in the placebo groups of 18-month clinical trials.
| Trial | Placebo, N (analyzed) | 6-month change, mean (SD) | 12-month change, mean (SD) | 18-month change, mean (SD) | ADAS-cog effect size, 18-mo, mean/SD | CDRsb change, mean (SD) | CDRsb effect size, mean/SD | ADCS-ADL change, mean (SD) | Dropouts |
|---|---|---|---|---|---|---|---|---|---|
| Atorvastatin/Pfizer | 317 | 0.78* | 4.12* | 6.78* | — | Not reported | n.a. | — | 24.5% |
| Simvastatin/NIA ADCS | 202 (190) | 2.35 (5.91) | 5.37 (6.97) | 8.14 (8.68) | 0.94 | Not done | — | 9.6 (13.9) | 27.2% |
| B vitamins/NIA ADCS | 169 (161) | 1.72 (4.74) | 4.46 (6.32) | 6.54 (8.17) | 0.80 | 2.51 (2.57) | 0.98 | 10.0 (11.1) | 17.2% |
| Xaliproden/EFC2724/international trial/Sanofi-Aventis† | 727 (698) | 1.12 (5.86) | 3.36 (7.66) | 5.49 (9.39) | 0.58 | 2.55 (3.03) | 0.84 | 10.3 (13.0)† | 26% |
| Xaliproden/EFC2946/NA trial/Sanofi-Aventis† | 648 (621) | 1.04 (5.24) | 2.41 (6.65) | 4.34 (8.56) | 0.51 | 2.05 (2.82) | 0.73 | 7.2 (11.1)† | 41% |
| Tramiprosate/NA trial/Bellus | 341 (265 ADAS) | 2.27 (6.12) | 4.84 (7.85) | 7.36 (9.28) | 0.79 | 2.50 (3.04) | 0.82 | — | 22.7% |
| Tarenflurbil/US trial/Myriad‡ | 809 (743) | 1.58 (5.09) | 3.81 (6.99) | 6.44 (8.69) | 0.74 | 2.43 (3.12) | 0.78 | 9.7 (14.0) | 33% |
| Tarenflurbil/international trial/Myriad‡ | 420 (403) | 1.49 (5.32) | 3.92 (7.08) | 5.85 (8.86)§ | 0.66 | 2.74 (3.17)§ | 0.86 | 11.4 (13.0) | 26.7%§ |
| Bapineuzumab/Elan, phase II | 110 (107) ‖ | n.a. | n.a. | 9.10 (8.33) | 1.09 | 2.99 (2.92) | 1.02 | — | 21% |
NOTE. Methods of estimating ADAS-cog and CDR-sb changes differ among trials; some use the end point, a repeated-measures analysis of variance with end point, and/or imputed last observations. Data were taken from publications, presentations at meetings, handouts to financial analysts, websites, or provided by the sponsors.
ADAS-cog change was estimated from a graphic depicting the change scores.
Xaliproden trials were primarily assessed by slope analyses; placebo group slopes for ADAS-cog in trial EFC2724 was 4.48/y (0.28 SE), and trial EFC2946 was 3.74/y (0.28 SE).
Tarenflurbil was assessed on an 80-point ADAS-cog scale as the primary outcome. Change scores for the US trial were 1.73 (5.74 SD), 4.28 (7.50), 7.08 (9.24) at 6, 12, and 18 months, respectively, and slope was 5.06/y (0.27 SE); change scores for the international trial were 1.57 (6.13), 4.45 (7.82), 6.30 (9.55) at 6, 12, and 18 months, and slope was 5.55/y (0.38 SE).
Sponsor terminated trial early; dropouts shows rate at 15 months.
Pooled from four dosing cohorts of 60 patients each, of which approximately 28 in each cohort were placebo-treated.
For comparison purposes, 186 participants in the AD Neuroimaging Initiative with mild AD, ie, MMSE from 21 to 26, showed baseline ADAS-cog scores of 18.7 (6.3) and change scores at 12 months and 24 months of 4.3 (6.4) and 9.9 (9.2), respectively, and baseline CDRsb 4.36 (1.61) and change scores at 12 months and 24 months of 1.54 (2.13) and 3.6 (2.90), respectively.