Table 2.
PK and PD parameters for crizanlizumab at starting dose (week 1 day 1) and at steady state (week 15 day 1) in PAS1
| Crizanlizumab, 5.0 mg/kg, N = 41 | Crizanlizumab, 7.5 mg/kg, N = 11 | |
|---|---|---|
| Wk 1 d 1 | ||
| AUCd15 (h × μg/mL), n | 37 | 10 |
| Mean (SD) | 13 000 (2 770) | 19 800 (4 490) |
| CV% | 21.3 | 22.7 |
| Cmax (μg/mL), n | 40 | 10 |
| Mean (SD) | 99.9 (29.6) | 174 (49.9) |
| CV% | 29.6 | 28.7 |
| Tmax (h), n | 40 | 10 |
| Median (range) | 1.5 (0.4-26.1) | 1.1 (0.6-23.6) |
| PD-AUCd15 (h%), n | 37 | 10 |
| Mean (SD) | 33 200 (1 800) | 33 200 (2 530) |
| CV% | 5.4 | 7.6 |
| Wk 15 d 1 (steady state) | ||
| AUCtau (h × μg/mL), n | 35 | 9 |
| Mean (SD) | 20 900 (4 810) | 27 800 (2 780) |
| CV% | 23.0 | 10.0 |
| Cmax (μg/mL), n | 35 | 10 |
| Mean (SD) | 125 (36.1) | 168 (34.2) |
| CV% | 28.9 | 20.4 |
| Tmax (h), n | 35 | 10 |
| Median (range) | 1.9 (0.6-6.3) | 3.0 (0.6-23.4) |
| T½ (h), n | 35 | 10 |
| Mean (SD) | 269 (84.8) | 325 (57.7) |
| PD-AUCd29 (h%), n | 32 | 10 |
| Mean (SD) | 67 500 (5 900) | 61 600 (10 900) |
| CV% | 8.7 | 17.6 |
AUCd15, area under the curve from time 0 to the last measurable concentration sampling time at starting dose; AUCtau, area under the curve from time 0 to the last measurable concentration sampling time at steady state; Cmax, maximum observed serum drug concentration after dose administration; CV%, coefficient of variation; PD-AUCd15, area under the curve from time 0 to the last measurable PD sampling time at starting dose; PD-AUCd29, area under the curve from time 0 to the last measurable PD sampling time at steady state; Tmax, time to reach maximum observed serum drug concentration after dose administration; T½, elimination half-life associated with the terminal slope of a semilogarithmic scale.