TABLE 2.
Summary statistics of key PK parameter estimates, stratified by study phase
| Variable | Phase 1 (n = 200)
|
Phase 2/3 (n = 360)
|
||
|---|---|---|---|---|
| Mean (SD) | Median (min-max) | Mean (SD) | Median (min-max) | |
| CL (liter/h) | 0.351 (0.109) | 0.350 (0.121-0.702) | 0.601 (0.204) | 0.584 (0.172-1.45) |
| Vc (liter) | 5.19 (1.27) | 5.04 (2.37-13.8) | 7.10 (2.46) | 6.79 (1.17-18.3) |
| t1/2α (h) | 2.56 (0.653) | 2.48 (1.23-4.78) | 2.04 (0.440) | 2.04 (0.910-4.08) |
| t1/2β (h) | 27.0 (11.5) | 25.4 (9.38-99.6) | 31.2 (11.4) | 29.2 (8.37-86.3) |
| t1/2γ (h) | 318 (59.1) | 314 (191-584) | 393 (73.5) | 394 (142-602) |
| AUC0-24 (μg·h/ml)a | 252 (78.6) | 240 (104-614) | 146 (63.7) | 133 (42.2-618) |
| Cmax (μg/ml)a | 35.7 (9.09) | 34.5 (20.4-80.0) | 28.5 (12.2) | 25.9 (10.9-131) |
| Cmin (μg/ml)a | 4.11 (1.80) | 3.65 (1.23-10.2) | 1.99 (1.10) | 1.74 (0.540-9.81) |
a
AUC0-24, Cmax, and Cmin have been normalized to a dose of 200 mg for those subjects of ≤110 kg and to a dose of 300 mg for those subjects of >110 kg.