Table 2.
Pharmacodynamic parameters of glycine in CSF
| PD parameter | N | BI 425809 5 mg | N | BI 425809 10 mg | N | BI 425809 25 mg | N | BI 425809 50 mg |
|---|---|---|---|---|---|---|---|---|
| Ratio of AUECdiff, 0–14, %a | 6 | 16.0 (17.4) | 6 | 37.0 (12.1) | 6 | 53.0 (30.5) | 5 | 47.0 (35.3) |
| E max, % | 6 | 35.3 (26.4) | 6 | 62.3 (15.3) | 8 | 136 (107) | 5 | 91.9 (89.9) |
| t max, hb | 6 | 6.5 (2.0–14.0) | 6 | 10.0 (6.0–14.0) | 8 | 6.2 (3.1–10.7) | 5 | 8.1 (6.0–14.1) |
| E 14, % | 6 | 18.0 (32.1) | 6 | 39.8 (14.5) | 6 | 60.9 (60.7) | 5 | 50.6 (33.8) |
| E 312, % | 4 | 1.17 (24.3) | 4 | 57.0 (48.3) | 6 | 37.9 (45.8) | 5 | 123 (52.5) |
All values are mean (SD) unless otherwise stated. AUECdiff, 0–14, ratio between AUECtreatment (area under the biomarker effect vs. time curve on treatment during the given interval) and AUECbase (baseline area under the biomarker effect vs. time curve during the given interval); CSF, cerebrospinal fluid; E 14, effect of glycine at the time point 14 hours after the first dose; E 312, effect of glycine at the time point 312 hours before the last dose is given; E max, maximum effect of glycine after the first dose; t max, time from dosing to maximum measured concentration of BI 425809; PD, pharmacodynamic.
aThe mean of the three glycine CSF pre‐dose levels was taken as a baseline value for the calculation of the AUECdiff, 0–14 parameter up to the last sampling point; bmedian (minimum‐maximum).