Table 1.
Summary of studies included in axitinib population pharmacokinetic analysis
| Study | Study design | Enrolled/analyzed (n) | Treatment (for those included in analysis) | Full PK sampling time points post dosing (h) |
|---|---|---|---|---|
| 1 [14] | R, SB, 2-way CO, DDI with ketoconazole | 35/32*† | 5 mg, oral, Form IV, o/n fast | Pre-dose (0), 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 |
| 2 [15] | OL, food effect on PK | 42/41‡ | Tx 1: 5 mg, oral, Form IV, o/n fast | 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 |
| Tx 2: 5 mg, oral, Form IV, fed | ||||
| 3 | OL, 2-way CO, absolute bioavailability study | 16/16 | Tx 1: 5 mg, Form IV, oral, o/n fast | 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 |
| Tx 2: 1 mg, Form IV, i.v., o/n fast | ||||
| Tx 3: 5 mg, Form IV, oral, fed | ||||
| 4 | R, OL, CO, relative bioavailability study | 40/20§ | 5 mg, oral, Form IV, o/n fast | 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 |
| 5 | R, OL, 2-sequence, 3-period CO, bioequivalence study | 40/40 | 5 mg, oral, Form IV, o/n fast | 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32 |
| 6 [16] | R, OL, 2-period, 2-Tx CO, | 40/40† | 5 mg, oral, Form IV, o/n fast | 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32 |
| DDI with rifampin | ||||
| 7 | R, OL, 4-sequence, 4-period, CO, relative bioavailability study | 56/54¶ | Tx 1: 5 mg, oral, Form IV, fed | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 32 |
| Tx 2: 5 mg, oral, Form XLI, fed | ||||
| 8 [18] | OL, PG, subjects with normal hepatic function or mild or moderate hepatic impairment | 24/8** | 5 mg, oral, Form IV, fed | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96, 144 |
| 9 | R, OL, 4-sequence, 4-period, CO, relative bioavailability study | 20/20 | 5 mg, oral, Form IV, fed | 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48 |
| 10 | R, OL, 2-sequence, 4-period, CO, bioequivalence study | 68/66* | 5 mg, oral, Form IV, o/n fast | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 |
Reasons for excluding individual data from analysis:
*
Did not receive axitinib;
†
Only data following administration of axitinib alone were included in the analysis;
‡
Not completed the study;
§
Received axitinib dose <5 mg in a spray-dried dispersion;
¶
Received axitinib in a spray-dried dispersion;
**
Due to impaired hepatic function. CO, crossover; DDI, drug–drug interaction; i.v., intravenous; OL, open-label; o/n, overnight; PG, parallel-group; PK, pharmacokinetics; R, randomized;SB, single-blind; Tx, treatment.