Table 3.
Summary of PK Parameters of Capmatinib Before and After Coadministration of Itraconazole or Rifampicin
| AUCinf (ng · h/mL) | AUClast (ng · h/mL) | Cmax (ng/mL) | tmax a (h) | CL/F (L/h) | t1/2 (h) | |
|---|---|---|---|---|---|---|
| Inhibition cohort | ||||||
| Capmatinib | n = 25 | n = 26 | n = 26 | n = 26 | n = 25 | n = 25 |
| Mean (CV%) | 5500 (27.1) | 5430 (27.0) | 1380 (40.4) | 1.00 (0.505–4.00) | 39.6 (33.4) | 9.29 (46.8) |
| Geometric mean (geometric CV%) | 5280 (30.6) | 5220 (30.6) | 1260 (46.9) | 37.9 (30.6) | 8.29 (53.7) | |
| Capmatinib + itraconazole | n = 22 | n = 22 | n = 22 | n = 22 | n = 22 | n = 22 |
| Mean (CV%) | 7680 (24.3) | 7660 (24.5) | 1410 (41.5) | 2.00 (0.495–4.01) | 27.8 (28.1) | 6.34 (32.8) |
| Geometric mean (geometric CV%) | 7450 (26.4) | 7430 (26.5) | 1290 (48.6) | 26.8 (26.4) | 6.05 (31.3) | |
| Induction cohort | ||||||
| Capmatinib | n = 24 | n = 25 | n = 25 | n = 25 | n = 24 | n = 24 |
| Mean (CV%) | 11 600 (24.1) | 12 100 (34.5) | 3330 (41.4) | 0.994 (0.461–3.00) | 36.4 (23.7) | 11.2 (63.2) |
| Geometric mean (geometric CV%) | 11 300 (24.3) | 11 600 (30.3) | 3070 (43.0) | 35.4 (24.3) | 9.71 (55.9) | |
| Capmatinib + rifampicin | n = 18 | n = 23 | n = 23 | n = 23 | n = 18 | n = 18 |
| Mean (CV%) | 4050 (32.6) | 3860 (31.3) | 1460 (43.4) | 0.994 (0.478–2.00) | 107 (26.1) | 11.1 (35.2) |
| Geometric mean (geometric CV%) | 3890 (29.4) | 3720 (27.0) | 1350 (41.8) | 103 (29.4) | 10.3 (40.8) |
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; CL/F, apparent total body clearance of drug from the plasma; Cmax, maximum plasma drug concentration; CV, coefficient of variation; PK, pharmacokinetic; t1/2, terminal‐phase half‐life; tmax, time to reach maximum plasma drug concentration; Vz/F, apparent volume of distribution during the terminal phase.
n = number of subjects with corresponding evaluable PK parameters.
a
Tmax data are shown as median (range).