TABLE 3.
MK-2206 Protocol 002 Preliminary Results: Summary PK Parameter Values Following Multiple QW Doses of 90, 135, 150, 200, 250 and 300mg of MK-2206 in Male and Female Oncology Patients
| QW Dose (mg) | N (Day 1, Day last) | AUC0-168h (nmol × h/L) Mean ± SD (%CV) | Cmax (nmol/L) Mean ± SD (%CV) | C48h (nmol/L) Mean ± SD | Tmax (h)a | Apparent Terminal t1/2 (h)b | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 | Last Day | Last Day / Day1 Ratioc | Day 1 | Last Day | Last Day / Day1 Ratioc | Day 1 | Last Day | Last Day / Day1 Ratioc | Day 1 | Last Day | Last Day | ||
| 90 | 3, 3 | 6510 ± 3810 (59%) | 10600 ± 7520 (71%) | --d | 81.7 ± 42.4 (52%) | 153 ± 98.0 (64%) | --d | 50.9 ± 38.2 | 79.3 ± 33.7 | 1.61 | 6.0 (4.0-10.0) | 4.0 (4.0-4.0) | 71.6 ± 12.2 |
| 135 | 5, 4 | 12000 ± 4610 (38%) | 20700 ± 8780 (42%) | 1.91 | 199 ± 98.9 (50%) | 352 ± 210 (60%) | 1.95 | 90.3 ± 25.1 | 158 ± 59.2 | 1.86 | 4.0 (4.0-10.0) | 5.0 (4.0-24.0) | 88.9 ± 26.9 |
| 150 | 2, 1 | 20700 | 22600 | --d | 337 | 346 | --d | 155 | 185 | --d | (4.0-10.0) | 4.0 | 64.4 |
| 200 | 17, 13 | 16400 ± 5470 (33%) | 23500 ± 14700 (63%) | 1.54 | 264 ± 75.8 (29%) | 345 ± 199 (58%) | 1.33 | 121 ± 47.4 | 187 ± 113 | 1.49 | 6.0 (4.0-10.0) | 6.0 (4.0-24.0) | 75.1 ± 14.7 |
| 250 | 3, 1 | 14000 ± 2950 (21%) | 10700 | --d | 231 ± 39.1 (17%) | 169 | --d | 103 ± 19.6 | 74.8 | --d | 6.0 (4.0-6.0) | 4.0 | 53.7 |
| 300 | 3, 0 | 27700 ± 3320 (12%) | --d | --d | 466 ± 123 (26%) | --d | --d | 253 | --d | --d | 4.0 (4.0-6.0) | --d | --d |
a
Median (min - max)
b
Harmonic mean ± pseudo SD
c
Geometric mean
d
Summary statistics not provided due to insufficient data
Abbreviations: AUC, area under the concentration-time curve; Cmax: maximum measured plasma concentration; C48hr, plasma concentration 48 hours following dose (trough concentration); Tmax, time from dosing to maximum plasma concentration; t1/2, half-life; SD, standard deviation