Table 2.
Plasma PK Parameters of Brigatinib With (Test Condition) and Without (Reference Condition) Coadministration of Gemfibrozil, Itraconazole, and Rifampin
| Study Arm/Parameter | Test Condition | Reference Condition | Geometric LS Mean Ratio (90%CI) (Test vs Reference) | |
|---|---|---|---|---|
| Gemfibrozil DDI arm | ||||
| n = 19 | n = 20 | 0.59 (0.54‐0.65) | ||
| Cmax, ng/mL | Geometric mean (% CV) | 198.9 (35.8) | 347.8 (40.5) | |
| Mean (SD) | 209.7 (66.1) | 373.2 (140.9) | ||
| n = 19 | n = 20 | 0.85 (0.80‐0.91) | ||
| AUC0‐120, h·ng/mL | Geometric mean (% CV) | 5340 (27.5) | 6488 (34.2) | |
| Mean (SD) | 5520 (1432) | 6839 (2318) | ||
| n = 19 | n = 19 | 0.88 (0.83‐0.94) | ||
| AUC0‐inf, h·ng/mL | Geometric mean (% CV) | 5742 (25.7) | 6875 (33.9) | |
| Mean (SD) | 5913 (1451) | 7233 (2371) | ||
| n = 19 | n = 19 | 1.13 (1.06‐1.20) | ||
| CL/F, L/h | Geometric mean (% CV) | 15.7 (25.7) | 13.1 (33.9) | |
| Mean (SD) | 16.2 (4.3) | 13.8 (4.6) | ||
| n = 19 | n = 20 | Test ‐ Reference | ||
| tmax, h | Median (range) | 2.0 (1.0‐6.0) | 2.0 (1.0‐4.0) | 0.3 (–3.0 to 4.0) |
| n = 19 | n = 19 | |||
| t½, h | Mean (SD) | 34.3 (6.1) | 26.7 (4.0) | |
| Itraconazole DDI arm | ||||
| n = 20 | n = 20 | 1.21 (1.13‐1.30) | ||
| Cmax, ng/mL | Geometric mean (% CV) | 401.4 (38.4) | 331.3 (31.9) | |
| Mean (SD) | 428.7 (163.1) | 347.2 (111.9) | ||
| n = 20 | n = 20 | 1.82 (1.72‐1.93) | ||
| AUC0‐120, h·ng/mL | Geometric mean (% CV) | 11 178 (31.2) | 6139 (28.5) | |
| Mean (SD) | 11 690 (3697) | 6382 (1918) | ||
| n = 11 | n = 20 | 2.01 (1.84‐2.20) | ||
| AUC0‐inf, h·ng/mL | Geometric mean (% CV) | 13 501 (35.6) | 6452 (28.7) | |
| Mean (SD) | 14 235 (4822) | 6709 (2006) | ||
| n = 11 | n = 20 | 0.50 (0.45‐0.54) | ||
| CL/F, L/h | Geometric mean (% CV) | 6.67 (35.6) | 14.0 (28.7) | |
| Mean (SD) | 7.05 (2.54) | 14.46 (3.84) | ||
| n = 20 | n = 20 | Test ‐ Reference | ||
| tmax, h | Median (range) | 2.6 (1.5‐6.0) | 2.8 (1.5‐4.0) | 0.0 (–2.5 to 2.0) |
| n = 11 | n = 20 | |||
| t½, h | Mean (SD) | 44.9 (8.4) | 30.5 (6.8) | |
| Rifampin DDI arm | ||||
| n = 19 | n = 20 | 0.40 (0.37‐0.44) | ||
| Cmax, ng/mL | Geometric mean (% CV) | 333.9 (29.2) | 825.9 (31.2) | |
| Mean (SD) | 346.6 (94.9) | 863.3 (265.2) | ||
| n = 19 | n = 20 | 0.20 (0.19‐0.22) | ||
| AUC0‐120, h·ng/mL | Geometric mean (% CV) | 3019 (25.7) | 15 143 (33.8) | |
| Mean (SD) | 3111 (783) | 15 907 (4948) | ||
| n = 19 | n = 20 | 0.20 (0.18‐0.21) | ||
| AUC0‐inf, h·ng/mL | Geometric mean (% CV) | 3042 (25.8) | 15 616 (34.4) | |
| Mean (SD) | 3136 (793) | 16 429 (5195) | ||
| n = 19 | n = 20 | 5.11 (4.73‐5.51) | ||
| CL/F, L/h | Geometric mean (% CV) | 59.2 (25.8) | 11.5 (34.4) | |
| Mean (SD) | 61.0 (15.4) | 12.2 (4.3) | ||
| n = 19 | n = 20 | Test – Reference | ||
| tmax, h | Median (range) | 2.0 (1.0‐4.0) | 2.5 (1.5‐6.0) | –0.5 (–2.1 to 1.0) |
| n = 19 | n = 20 | |||
| t½, h | Mean (SD) | 23.7 (3.2) | 25.1 (4.1) | |
AUC0‐120 indicates area under the plasma concentration‐time curve from time 0 to 120 hours; AUC0‐inf, area under the plasma concentration‐time curve from time 0 to infinity; CL/F, apparent oral clearance; Cmax, peak plasma concentration; CV, coefficient of variation; DDI, drug‐drug interaction; LS, least squares; PK, pharmacokinetics; t½, elimination half‐life; tmax, time to peak plasma concentration.
Test = brigatinib + CYP inhibitor/inducer; Reference = brigatinib alone.