Table 2.
Summary of Noncompartmental Pharmacokinetic Parameters
| Parameter | Asfotase Alfa 0.5 mg/kg (n = 8) | Asfotase Alfa 2.0 mg/kg (n = 10) | Asfotase Alfa 3.0 mg/kg (n = 9) | |||
|---|---|---|---|---|---|---|
| Day 1 | Day 61 | Day 1 | Day 61 | Day 1 | Day 61 | |
| Cmax, U/L | 218 (24.1) | 743 (63.6) | 617 (51.8) | 1900 (53.6) | 915 (35.3) | 3600 (43.7) |
| tmax, d | 1.9 (0.5‐3.0) | 0.7 (0.0‐2.5) | 2.3 (1.5‐5.0) | 1.2 (0.0‐2.5) | 3.0 (1.5‐6.0) | 1.0 (0.3‐1.3) |
| AUClast, U × d/L | 588 (77.0) | NE | 3310 (60.6) | NE | 5620 (63.3) | NE |
| AUCinf, U × d/L | NE | NE | 5350 (45.6) | NE | 9030 (40.3) | NE |
| t½, d | NE | 5.1 (10.2) | 3.7 (16.4) | 4.6 (28.0) | 4.7 (17.9) | 5.5 (18.3) |
| λz, d−1 | NE | 0.135 (10.2) | 0.189 (16.4) | 0.150 (28.0) | 0.148 (17.9) | 0.125 (18.3) |
| CL/F, U/L | NE | NE | 18.8 (37.2) | NE | 22.1 (41.2) | NE |
| Vz/F, L | NE | NE | 99.1 (25.9) | NE | 150 (36.2) | NE |
| CtroughR | NE | 4.15 (35.3) | NE | 3.14 (65.5) | NE | 4.68 (33.6) |
λz, terminal elimination rate constant; AUCinf, area under the concentration‐time curve from time 0 to infinity; AUClast, area under the concentration‐time curve from time 0 to time of the last observed concentration in a dosing interval; CL/F, apparent clearance after subcutaneous dosing; Cmax, maximum concentration in the dosing interval; CtroughR, ratio of concentration 48 hours after first dose to predose concentration on day 61 after multiple dosing; CV%, coefficient of variation; NE, not evaluable; t½, terminal elimination half‐life; tmax, time of maximum concentration in the dosing interval; Vz/F, apparent volume of distribution after subcutaneous dosing.
Geometric mean and geometric CV% were provided for all parameters except tmax, where median and range were provided.
NE: Due to the limited available data, several parameters were not evaluable or not evaluated. For all 3 dose cohorts, CtroughR was not evaluated because it is not a relevant PK parameter after a single dose else; see the Results section for explanations.