From: Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer’s disease
Placebo | LY 100 mg | LY 140 mg | P -value | |
---|---|---|---|---|
Annualized change in ADASCog11 | 4.75 ± 21.92 (n = 485) | 6.57 ± 25.57 (n = 482) | 5.48 ± 21.92 (n = 495) | 0.408 |
Annualized change in MMSE | −2.19 ± 3.65 (n = 396) | −2.56 ± 3.65 (n = 324) | −2.92 ± 3.65 (n = 303) | 0.159 |
Annualized change in FDG-PET SUVR | −0.06 ± 0.07 (n = 40) | −0.13 ± 0.21 (n = 42) | −0.1 ± 0.08 (n = 33) | 0.109 |
Annualized change in AV45 SUVR | 0.05 ± 0.11 (n = 18) | 0.02 ± 0.24 (n = 23) | 0.07 ± 0.23 (n = 18) | 0.794 |
Annualized change in ventricular volume | 4.07 ± 3.52 (n = 80) | 4.19 ± 3.92 (n = 74) | 5.68 ± 4.68 (n = 67) | 0.033 |
Annualized change in right hippocampal volume | −86.28 ± 73.86 (n = 74) | −91.08 ± 102.1 (n = 68) | −90.98 ± 71.1 (n = 64) | 0.926 |
Annualized change in left hippocampal volume | −68.85 ± 59.01 (n = 74) | −70.4 ± 90.81 (n = 68) | −91.0 ± 101.2 (n = 64) | 0.244 |
Annualized change in CSF Aβ40 | 87.66 ± 847 (n = 10) | −10.96 ± 1151 (n = 19) | −599 ± 1786 (n = 18) | 0.328 |
Annualized change in CSF Aβ42 | 10.96 ± 87.66 (n = 10) | −40.18 ± 109.6 (n = 19) | −36.5 ± 182.7 (n = 18) | 0.619 |
Annualized change in p-tau | 10.96 ± 7.31 (n = 10) | −7.31 ± 14.61 (n = 19) | −3.65 ± 10.96 (n = 18) | 0.009 |
Annualized change in total tau | 94.97 ± 116.9 (n = 10) | −43.83 ± 219.2 (n = 17) | 40.18 ± 127.8 (n = 18) | 0.101 |
Percentage change in plasma Aβ40 at week 52 | 4.77 ± 26.67 (n = 307) | −37.54 ± 109.3 (n = 264) | −47.76 ± 32.06 (n = 243) | <0.001 |
Percentage change in plasma Aβ42 at week 52 | 3.82 ± 20.75 (n = 309) | −5.4 ± 53.1 (n = 265) | −18.14 ± 33.0 (n = 245) | <0.001 |
Change in uric acid at week 76 | 0.18 ± 0.83 (n = 210) | −0.96 ± 1.08 (n = 179) | −0.88 ± 1.22 (n = 147) | <0.001 |
Change in albumin at week 76 | 0 ± 0.25 (n = 210) | −0.09 ± 0.31 (n = 179) | −0.09 ± 0.3 (n = 147) | 0.002 |
Change in eosinophils at week 76 | −0.001 ± 0.09 (n = 207) | 0.05 ± 0.17 (n = 179) | 0.06 ± 0.14 (n = 143) | <0.001 |
Gastrointestinal symptoms | 153 (31.5%) | 169 (34.9%) | 193 (38.8%) | 0.057 |
Skin disorder incidence | 105 (21.6%) | 220 (45.4%) | 269 (54%) | <0.001 |
Skin cancer incidence | 8 (1.7%) | 51 (10.5%) | 56 (11.2%) | <0.001 |
Infection incidence | 156 (32.1%) | 188 (38.8%) | 220 (44.2%) | <0.001 |
AUC | 5,316 ± 1,525 (n = 480) | 7,235 ± 2233 (n = 494) | <0.001 | |
Cmax | 1,105 ± 260 (n = 480) | 1,508 ± 384 (n = 494) | <0.001 |