Table 3.
Change from baseline of cerebrospinal fluid and plasma amyloid‐β isoforms AUEC(0,24 h) (pg ml‐1 h) on day 14 (PD analysis set)
| Absolute AUEC (0,24 h) | Adjusted mean change from baseline * AUEC(0,24 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 | 47289.5 | 52090.0 | 5709.89 | −4374.08 (−19372.94, 10624.79) | 0.557 | 1.11 | 0.96 | 0.73, 1.26 | 0.767 |
| Placebo, n = 18 | 42604.7 | 53547.5 | 10083.97 | 1.16 | |||||
| Amyloid‐β 1–40 | |||||||||
| LCZ696, n = 17 | 356264.3 | 412403.2 | 58593.53 | 20441.88 (−71901.30, 112785.06) | 0.655 | 1.16 | 1.07 | 0.86, 1.34 | 0.546 |
| Placebo, n = 18 | 342756.1 | 383226.1 | 38151.65 | 1.08 | |||||
| Amyloid‐β 1–38 | |||||||||
| LCZ696, n = 17 | 51304.9 | 81642.5 | 30492.92 | 21916.37 (−2767.16, 41065.58) | 0.026 | 1.58 | 1.43 | 1.10, 1.86 | 0.010 |
| Placebo, n = 18 | 49484.2 | 58207.5 | 8576.55 | 1.11 | |||||
| Plasma | |||||||||
| Amyloid‐β 1–40 | |||||||||
| LCZ696, n = 17 | 1528.9 | 2335.9 | 806.96 | 801.09 (676.15, 926.03) | <0.001 | 1.53 | 1.52 | 1.43, 1.62 | <0.001 |
| Placebo, n = 18 | 1533.4 | 1539.2 | 5.87 | 1.01 | |||||
*
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