Table 2.
Change from baseline of cerebrospinal fluid and plasma amyloid‐β isoforms AUEC(0,36 h) (pg ml‐1 h) on day 14 (PD analysis set)
| Absolute AUEC(0,36 h) | Adjusted mean change from baseline * AUEC(0,36 h) | Estimated treatment difference * (95% CI) | P value * | Adjusted geometric mean † | Estimated treatment ratio † (LCZ696 : placebo) | 95% CI of ratio † (LCZ696 : placebo) | P value † | ||
|---|---|---|---|---|---|---|---|---|---|
| Baseline | Day 14 | ||||||||
| CSF | |||||||||
| Amyloid‐β 1–42 | |||||||||
| LCZ696, n = 17 | 73167.4 | 81043.7 | 9703.18 | −5754.79 (−32122.78, 20613.20) | 0.660 | 1.12 | 0.98 | 0.73, 1.34 | 0.919 |
| Placebo, n = 18 | 66702.1 | 83885.4 | 15457.97 | 1.14 | |||||
| Amyloid‐β 1–40 | |||||||||
| LCZ696, n = 17 | 551061.5 | 630561.3 | 82414.33 | 16332.96 (−135541.51, 168207.42) | 0.828 | 1.14 | 1.05 | 0.82, 1.34 | 0.702 |
| Placebo, n = 18 | 536543.5 | 605377.5 | 66081.37 | 1.09 | |||||
| Amyloid‐β 1–38 | |||||||||
| LCZ696, n = 17 | 79256.6 | 126201.7 | 47183.26 | 31549.18 (−1100.04, 64198.40) | 0.058 | 1.58 | 1.42 | 1.05, 1.91 | 0.023 |
| Placebo, n = 18 | 76621.5 | 92480.6 | 15634.09 | 1.11 | |||||
| Plasma | |||||||||
| Amyloid‐β 1–40 | |||||||||
| LCZ696, n = 17 | 2287.0 | 3430.9 | 1143.76 | 1144.05 (946.70, 1341.40) | <0.001 | 1.50 | 1.50 | 1.41, 1.59 | <0.001 |
| Placebo, n = 18 | 2296.9 | 2296.4 | −0.29 | 1.00 | |||||
*
Adjusted means (SE), 95% CIs for mean difference and P values are determined from a linear model on change from baseline AUEC with treatment as fixed effect and baseline AUEC as a continuous covariate.
†
The change from baseline AUEC in log scale was analyzed using a fixed effect model with treatment as fixed effect and log transformed baseline AUEC as continuous covariate.
AUEC, area under the effect curve; CI, confidence interval; CSF, cerebrospinal fluid; PD, pharmacodynamic; SE, standard error