Table 4.
Summary of PK Parameters of CMN288 Before and After Coadministration of Itraconazole or Rifampicin With Capmatinib
| AUCinf (ng · h/mL) | AUClast (ng · h/mL) | Cmax (ng/mL) | tmax a (h) | MR (AUCinf) | MR (AUClast) | MR (Cmax) | |
|---|---|---|---|---|---|---|---|
| Inhibition cohort | |||||||
| Capmatinib | n = 26 | n = 26 | n = 26 | n = 26 | n = 25 | n = 26 | n = 26 |
| Mean (CV%) | 3870 (35.5) | 3810 (36.2) | 736 (47.0) | 1.01 (0.968–6.02) | 0.699 (25.4) | 0.685 (27.5) | 0.533 (30.5) |
| Geometric mean (geometric CV%) | 3640 (36.6) | 3580 (37.6) | 665 (48.7) | 0.677 (26.1) | 0.660 (29.1) | 0.506 (34.7) | |
| Capmatinib + itraconazole | n = 22 | n = 22 | n = 22 | n = 22 | n = 22 | n = 22 | n = 22 |
| Mean (CV%) | 4600 (35.7) | 4570 (36.0) | 682 (50.8) | 2.00 (0.983–4.01) | 0.572 (25.1) | 0.570 (25.6) | 0.462 (29.2) |
| Geometric mean (geometric CV%) | 4290 (42.3) | 4260 (43.2) | 590 (63.8) | 0.554 (26.2) | 0.552 (26.9) | 0.442 (31.6) | |
| Induction cohort | |||||||
| Capmatinib | n = 25 | n = 25 | n = 25 | n = 25 | n = 24 | n = 25 | n = 25 |
| Mean (CV%) | 7710 (30.1) | 7600 (30.2) | 1610 (39.2) | 0.994 (0.957–3.00) | 0.634 (25.2) | 0.627 (25.1) | 0.492 (30.8) |
| Geometric mean (geometric CV%) | 7420 (28.4) | 7310 (28.4) | 1500 (41.4) | 0.615 (25.5) | 0.609 (25.1) | 0.470 (31.1) | |
| Capmatinib + rifampicin | n = 23 | n = 23 | n = 23 | n = 23 | n = 18 | n = 23 | n = 23 |
| Mean (CV%) | 5360 (32.1) | 5320 (32.5) | 1690 (38.1) | 0.998 (0.924–3.00) | 1.37 (26.0) | 1.35 (25.0) | 1.17 (28.9) |
| Geometric mean (geometric CV%) | 5110 (31.9) | 5070 (32.3) | 1570 (39.8) | 1.33 (28.6) | 1.31 (26.4) | 1.13 (28.7) |
AUCinf, area under the plasma concentration–time curve from time 0 to infinity; AUClast, area under the plasma concentration–time curve from time 0 to the last quantifiable concentration point; Cmax, maximum plasma drug concentration; CV, coefficient of variation; MR, metabolite‐to‐parent drug ratio/metabolic ratio; PK, pharmacokinetic; tmax, time to reach maximum plasma drug concentration.
n = number of subjects with corresponding evaluable PK parameters.
a
Tmax data are shown as median (range).