Table 3.
Mean (SD) PTC299 Pharmacokinetic Parameters: Study 2—Stage 1 and Stage 2
| Stage 1 | Stage 2 | |||||||
|---|---|---|---|---|---|---|---|---|
| PTC299 Dose mg/kg/dose Twice Daily | PTC299 Dose mg/kg/dose 3 Times Daily | |||||||
| 0.3 n = 6 | 0.6 n = 6 | 1.2 n = 6 | 1.6 n = 6 | |||||
| Parameter, Units | Day 1 | Day 7 | Day 1 | Day 7 | Day 1 | Day 7 | Day 1 | Day 7 |
| Tmax (after pm dose), h | 3.2 | 3.3 | 3.2 | 3.3 | 3.0 | 3.3 | 2.5 | 2.3 |
| (0.41) | (0.52) | (0.41) | (0.52) | (0.00) | (0.52) | (1.1) | (1.4) | |
| Cmax (after pm dose), μg/mL | 0.48 | 0.59 | 0.97 | 1.2 | 2.0 | 2.5 | 2.4 | 4.7 |
| (0.15) | (0.18) | (0.24) | (0.27) | (0.29) | (0.57) | (0.46) | (1.9) | |
| C24h, μg/mL | 0.094 | 0.21 | 0.26 | 0.54 | 0.41 | 0.85 | 1.3 | 2.4 |
| (0.04) | (0.09) | (0.10) | (0.21) | (0.17) | (0.32) | (0.40) | (0.62) | |
| AUC0–24, μg·h/mL | 4.3 | 8.4 | 10 | 19 | 18 | 33 | 37 | 79 |
| (1.2) | (2.8) | (2.6) | (4.9) | (4.0) | (9.4) | (5.9) | (19) | |
| Dose‐normalized Cmax, μg/mL/mg/kg | 0.79 | 0.99 | 0.81 | 0.97 | 0.82 | 1.03 | 0.51 | 0.98 |
| (0.24) | (0.29) | (0.20) | (0.22) | (0.12) | (0.24) | (0.10) | (0.38) | |
| Dose‐normalized AUC0–24, μg·h/mL/mg/kg | 7.2 | 14 | 8.4 | 16 | 7.5 | 14 | 7.7 | 16 |
| (2.0) | (4.7) | (2.2) | (4.1) | (1.6) | (3.9) | (1.2) | (4.0) | |
| t1/2, h | NC | 164 (9.7)a | NC | 210 (35)b | NC | 228 (58)b | NC | 225 (55)b |
| CL/F (mL/min) | NC | 88 (23) | NC | 83 (28) | NC | 81 (14) | NC | 69 (20) |
AUC0–24 h, area under the concentration–time curve from time zero to 24 hours postdose; C24, concentration at 24 hours after first daily dose; Cmax, maximum compound concentration; NC, not calculated; Tmax, time of maximum compound concentration; CL/F, nominal clearance (normalized for bioavailability).
Values represent male and female subjects combined.
a
n = 4. bn = 3.