Table 4.
Pharmacodynamic effects compared to placebo
| Outcome | Cohort 1 (n = 12) |
Cohort 2 (n = 12) |
Cohort 3 (n = 12) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DPZ placebo + EVP-6124 0.3 mg | DPZ placebo + EVP-6124 1 mg | DPZ placebo + EVP-6124 2 mg | DPZ placebo + EVP-6124 4 mg | DPZ 2.5 mg + EVP-6124 placebo | DPZ 2.5 mg + EVP-6124 0.3 mg | DPZ 2.5 mg + EVP-6124 1 mg | DPZ 2.5 mg + EVP-6124 2 mg | DPZ 5 mg + EVP-placebo | DPZ 5 mg + EVP-6124 0.3 | DPZ 5 mg + EVP-6124 1 mg | DPZ 5 mg + EVP-6124 2 mg | |
| Adaptive tracking (%) | −1.23 (−2.80, 0.34) P = .1200 | 0.03 (−1.56, 1.63) P = .9671 | −0.83 (−2.33, 0.67) P = .2691 | −0.26 (−1.76, 1.24) P = .7281 | 1.49 (0.20, 2.77) P = .0247 | −1.12 (−2.41, 0.17) P = .0855 | −1.00 (−2.31, 0.31) P = .1312 | −1.14 (−2.43, 0.14) P = .0796 | 0.72 (−0.76, 2.20) P = .3297 | −0.23 (−1.74, 1.28) P = .7616 | −0.02 (−1.52, 1.48) P = .9777 | −0.00 (−1.49, 1.48) P = .9985 |
| Body sway (mm)∗ | 7.1 (3.2, 18.6) P = .1796 | −0.3 (10.1, 10.5) P = .9471 | −1.7 (−11.3, 8.8) P = .7290 | 11.6 (0.7, 23.6) P = .0363 | 1.9 (−10.9, 16.6) P = .7767 | −4.4 (−16.0, 8.7) P = .4792 | −0.0 (−12.3 13.9) P = .9957 | 4.7 (−8.0, 19.1) P = .4786 | −7.6 (−16.7, 2.5) P = .1296 | 2.6 (−7.7, 14.1) P = .6260 | 5.4 (−5.1, 17.2) P = .3152 | −3.0 (−12.6, 7.7) P = .5561 |
| VVLT delayed word recall (number of words) | 0.4 (−0.9, 1.7) P = .5508 | 0.1 (−1.2, 1.4) P = .8959 | −1.1 (−2.3, 0.2) P = .0970 | −0.4 (−1.6, 0.9) P = .5755 | −0.4 (−1.5, 0.7) P = .4707 | 0.1 (−1.0, 1.2) P = .654 | 0.5 (−0.6, 1.6) P = .3988 | 0.3 (−0.7, 1.4) P = .5417 | −0.2 (−1.3, 0.8) P = .6466 | 0.2 (−0.9, 1.3) P = .7362 | 0.4 (−0.7, 1.5) P = .4469 | 1.2 (0.1, 2.3) P = .0327 |
| N-back, 0-back accuracy (%) | 0.02 (−0.04, 0.08) P = .5073 | 0.04 (−0.03, 0.10) P = .2318 | 0.05 (−0.01, 0.11) P = .0818 | 0.06 (0.00, 0.12) P = .0470 | 0.03 (−0.05, 0.11) P = .4512 | 0.04 (−0.04, 0.12) P = .3346 | 0.06 (−0.02, 0.14) P = .1629 | 0.01 (−0.07, 0.09) P = .8116 | 0.04 (−0.02, 0.10) P = .1614 | −0.05 (−0.11, 0.01) P = .1030 | 0.01 (−0.05, 0.07) P = .7496 | −0.03 (−0.10, 0.03) P = .2730 |
| N-back, 0-back reaction time (ms) | 8 (−12, 29) P = .4004 | −17 (−37, 4) P = .1085 | −5 (−25, 15) P = .6209 | −16 (−36, 4) P = .1151 | −24 (−48, 1) P = .0615 | −9 (−31, 13) P = .3889 | 13 (−9, 35) P = .2366 | 11 (−11, 33) P = .3189 | −18 (−36, −1) P = .0386 | −7 (−24, 11) P = .4388 | −6 (−24, 12) P = .5046 | 3 (−15, 20) P = .7511 |
| N-back, 1-back accuracy (%) | 0.02 (−0.05, 0.10) P = .5558 | 0.04 (−0.04, 0.12) P = .3062 | 0.08 (0.01, 0.16) P = .0337 | 0.05 (−0.03, 0.12) P = .2385 | −0.00 (−0.12, 0.11) P = .9598 | 0.04 (−0.08, 0.16) P = .5014 | 0.01 (−0.11, 0.12) P = .9269 | −0.01 (−0.13, 0.10) P = .8351 | 0.03 (−0.05, 0.11) P = .4286 | −0.04 (−0.12, 0.04) P = .3158 | −0.03 (−0.11, 0.05) P = .5004 | −0.09 (−0.17, −0.01) P = .0273 |
| N-back, 2-back accuracy (%) | −0.02 (−0.11, 0.07) P = .6878 | 0.01 (−0.08, 0.10) P = .8796 | 0.03 (−0.06, 0.13) P = .4557 | −0.02 (−0.11, 0.07) P = .7181 | 0.04 (−0.08, 0.17) P = .5034 | 0.01 (−0.11, 0.14) P = .8346 | −0.06 (−0.19, 0.06) P = .3162 | −0.14 (−0.26, −0.01) P = .0336 | 0.02 (−0.08, 0.11) P = .7469 | −0.03 (−0.12, 0.07) P = .5790 | −0.04 (−0.14, 0.05) P = .3887 | −0.08 (−0.18, 0.01) P = .0800 |
| N-back, 2-back reaction time (ms) | −5 (−36, 25) P = .7210 | −3 (−33, 28) P = .8693 | 1 (−29, 31) P = .9305 | −8 (−39, 22) P = .5733 | −27 (−70, 16) P = .2115 | 27 (−16, 70) P = .2057 | 35 (−8, 79) P = .1070 | 41 (−2, 85) P = .0625 | 35 (−1, 70) P = .0541 | −42 (−77, −8) P = .0187 | −20 (−55, 15) P = .2513 | −15 (−49, 19) P = .3722 |
| Simple reaction time test (%)∗ | 3.3 (−7.0, 14.6) P = .5380 | −1.5 (−11.5, 9.8) P = .7844 | −1.1 (−10.9, 9.8) P = .8319 | 5.2 (−5.2, 16.7) P = .3279 | −14.6 (−26.2,−1.3) P = .0336 | 2.7 (−10.5, 17.9) P = .6933 | 2.5 (−10.9, 17.8) P = .7246 | 6.4 (−7.6, 22.6) P = .3786 | −3.1 (−9.2, 3.4) P = .3379 | 0.0 (−6.3, 6.8) P = .9947 | −0.2 (−6.5, 6.6) P = .9632 | 0.0 (−6.3, 6.7) P = .9999 |
| EEG alpha Fz-Cz (uV)∗ | 6.8 (−1.4, 15.7) P = .1053 | 12.0 (3.1, 21.7) P = .0087 | 7.3 (−0.9, 16.2) P = .0818 | 5.3 (−2.8, 14.0) P = .1987 | 5.8 (−7.5, 21.0) P = .4030 | −4.4 (−16.5, 9.5) P = .5065 | 3.1 (−10.1, 18.3) P = .6505 | −6.6 (−18.4, 6.7) P = .3051 | 4.0 (−13.2, 24.6) P = .6615 | −9.6 (−25.2, 9.4) P = .2909 | −5.3 (−21.4, 14.1) P = .5556 | −15.2 (−29.3, 1.8) P = .0759 |
| Saccadic inaccuracy (%) | 0.6 (−0.2, 1.4) P = .1224 | 0.0 (−0.8, 0.8) P = .9525 | −0.1 (−0.9, 0.6) P = .7196 | 0.3 (−0.5, 1.1) P = .4213 | −1.4 (−2.7, −0.1) P = .0311 | 1.3 (0.1, 2.6) P = .0388 | 1.4 (0.0, 2.7) P = .0474 | 0.8 (−0.5, 2.0) P = .2132 | 0.0 (−0.9, 1.0) P = .9433 | −0.2 (−1.2, 0.8) P = .7336 | 0.5 (−0.5, 1.5) P = .3449 | 0.2 (−0.7, 1.2) P = .6470 |
| Saccadic reaction time (ms) | −4 (−13, 5) P = .4018 | −2 (−12, 7) P = .5871 | −3 (−12, 6) P = .4605 | 3 (−6, 11) P = .5707 | −4 (−20, 11) P = .5539 | 8 (−6, 23) P = .2495 | 3 (−12, 18) P = .6847 | 11 (−4, 26) P = .1466 | −11 (−20, −2) P = .0190 | −4 (13, 5) P = .3548 | 12 (3, 22) P = .0190 | 1 (−8, 10) P = .8674 |
Abbreviations: DPZ, donepezil; VVLT, Visual Verbal Learning Test.
∗
Back translated from log; effect parameter and 95% confidence intervals are presented; effect parameters represent differences compared to placebo estimated by the statistical model that includes random factors for subject, time, subject by time and treatment, and adjusts for pre-values.