TABLE 3.
| Study 2 | N | Day 1 | Day 2 | Day 4 | Day 7 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cmax (ng/mL) | AUC0-24 (ng·h/ mL) | Tmax (h) | Cmax (ng/mL) | AUC0-24 (ng·h/ mL) | Tmax (h) | Cmax (ng/mL) | AUC0-24 (ng·h/ mL) | Tmax (h) | Cmax (ng/mL) | AUC0-24 (ng·h/ mL) | Tmax (h) | T½ (h) | CL (mL/h/kg) | Vz (L/kg) | ||
| Cohort A 1,500/900 mg |
5 | 17,436 [7.88] | 240,839 [9.77] |
11.0 [11.0–12.2] |
– | – | – | 16,193 [8.59] | 294,808 [9.03] | 3.00 [2.00–3.92] |
17,178 [9.53] | 305,887 [11.6] | 3.03 [2.92–3.50] | 67.9 [31.0]a | 32.1 [15.3] | 3.42 [23.4]a |
| Cohort B 900/900 mg |
2 | 10,571 [34.5] | 133,655 [32.6] | 7.50 [3.00–12.0] |
13,517 [15.8] | 236,001 [22.2] | 12.0 [12.0–12.0] |
16,733 [12.71] | 280,660 [14.5] | 3.04 [3.00–3.08] |
14,892 [4.75] | 270,745 [7.87] | 3.01 [3.00–3.02] | 89.0b | 31.6 [4.52] | 4.18b |
| Cohort C 1,000/900 mg |
1 | 13,700 | 164,806 | 12.0 [12.0–12.0] |
– | – | – | 18,700 | 238,666 | 3.00 [3.00–3.00] |
19,000 | 289,695 | 3.00 [3.00–3.00] | 69.0 | 33.5 | 3.34 |
| Cohort D 1,000/750 mg |
6 | 14,255 [20.1] | 202,026 [19.7] | 12.0 [12.0–12.0] |
– | – | – | 16,139 [15.0] | 254,095 [12.5] | 3.02 [2.00–3.22] |
16,859 [13.6] | 273,327 [12.0] | 3.01 [2.00–3.03] | 51.7 [24.5] | 29.9 [16.9] | 2.23 [41.4] |
| Cohort E 1,000/850 mg |
4 | 14,150 [33.6] | 205,589 [26.1] | 12.1 [11.0–12.1] |
– | – | – | 17,740 [15.6] | 279,977 [13.8] | 3.00 [3.00–3.02] |
18,017 [14.00] | 300,755 [9.31] | 2.52 [2.00–3.08] | 58.8 [46.0] | 31.3 [15.3] | 2.66 [43.4] |
| Cohort F 1,000/900 mg |
6 | 12,316 [19.4] | 172,244 [15.6] | 12.0 [3.03–16.0] |
– | – | – | 17,018 [6.87] | 265,124 [10.0] | 3.01 [2.98–3.32] |
16,850 [11.0] | 263,509 [15.1] | 2.98 [0.00–8.00] | 75.1 [41.3] | 36.0 [15.2] | 3.90 [51.7] |
a
n = 3.
b
n = 1.
c
Data are presented as geometric mean [geometric %CV] except for Tmax for which the median [range] is reported.
d
Dash denotes that the parameter was not applicable to the study day.
e
AUC0-24, area under the concentration-time curve from time zero to 24 h postdose; AUC0-t, area under the concentration-time curve from zero to time t postdose; Cmax, maximum plasma concentration; %CV, percent coefficient of variation; IV, intravenous; FMGX, fosmanogepix; MGX, manogepix; CL, clearance; t1/2, terminal phase half-life; Tmax, time to maximum plasma concentration (Cmax); Vz, volume of distribution.