Table 4.
Phase 2 study of patients with myelofibrosis: sustained‐release ruxolitinib pharmacokinetic parameters at weeks 4 and 12
| Ruxolitinib 25 mg SR QD | Ruxolitinib 50 mg SR QD | Ruxolitinib 25 mg SR QODa | ||
|---|---|---|---|---|
| Parameters, Mean ± SD (Geometric Mean) | Week 4 (n = 36) | Week 12 (n = 18) | Week 12 (n = 11) | Week 12 (n = 5) |
| C min, nM | 32.9 ± 42.0 (NC) | 59.1 ± 49.3 (NC) | 70.0 ± 79.4 (NC) | 51.3 ± 94.9 (NC) |
| C max, nM | 411 ± 221 (371) | 464 ± 223 (419) | 730 ± 334 (664) | 407 ± 142 (387) |
| PT ratio | 40.1 ± 55.4 (20.4) | 11.7 ± 9.21 (9.30) | 28.5 ± 37.5 (15.8) | 45.9 ± 63.4 (16.84) |
| t ½, h | 7.21 ± 3.67 (6.37) | 8.46 ± 3.62 (7.66) | 6.12 ± 2.98 (5.44) | 16.3 ± 17.8 (8.90) |
| AUCt, nM·h | 2110 ± 1260 (1830) | 2590 ± 1320 (2290) | 4260 ± 1730 (3880) | 2370 ± 1060 (2180) |
| AUC0‐t, nM·h | 3320 ± 2280 (2750) | 4520 ± 2390 (3960) | 6670 ± 3410 (5870) | 4010 ± 2460 (3440) |
| CL/F, L/h | 34.8 ± 18.7 (29.6) | 23.6 ± 12.9 (20.6) | 32.2 ± 20.2 (27.8) | 27.5 ± 15.6 (23.4) |
| Vz/F, L | 350 ± 212 (289) | 287 ± 190 (237) | 255 ± 156 (226) | 470 ± 540 (305) |
| Median (range) | ||||
| t max, h | 2.0 (1.0‐6.0) | 2.0 (0.5‐8.0) | 3.0 (1.0‐8.0) | 2.0 (0.5‐3.0) |
At week 4, there were 36 patients in the 25 mg SR QD group, 2 in the 5 mg IR BID group, and 2 who were not included (1 because of withdrawal from the study and 1 because of a dose interruption). At week 12, there were 18 patients in the 25 mg SR QD group, 11 in the 50 mg SR QD group, 7 in the 25/50 mg QOD group (5 patients took 25 mg SR and 2 took 50 mg SR that day), and 2 in the 5 mg IR BID group.
Abbreviations: AUCt, area under the concentration‐time curve at the last measurable concentration; AUC0‐t, area under the concentration‐time curve from time 0 to the last measurable concentration; BID, twice daily; C max, maximum plasma concentration; C min, minimum plasma concentration; CL/F, oral dose clearance; IR, immediate release; NC, not calculated; PT, peak‐trough; QD, once daily; QOD, every other day; SR, sustained release; t max, time to maximum plasma concentration; t ½, elimination half‐life; Vz/F, volume of distribution.
The 25 mg SR QOD regimen was 25/50 mg SR QOD with the 25 mg dose on the day of plasma concentration collection. The 25/50 mg QOD group that received 50 mg on the pharmacokinetic sampling day (n = 2) was not included in the table because of the small number of patients in this group.