TABLE 3.
Summary and statistical analysis of pharmacokinetic parameters for capmatinib by study group (pharmacokinetic analysis set)
| Parameter | Statistics | Normal (n = 9) | Mild (n = 6) | Moderate (n = 8) | Severe (n = 6) |
|---|---|---|---|---|---|
| AUClast (ng × h/mL) | Mean (SD) | 6930 (3350) | 4810 (944) | 5920 (1860) | 8510 (4410) |
| GM | 6190 | 4730 | 5660 | 7710 | |
| CV% GM | 55.2 | 20.7 | 32.5 | 50.1 | |
| AUCinf (ng × h/mL) | Mean (SD) | 6970 (3340) | 4870 (992) | 5960 (1890) | 8530 (4410) |
| GM | 6240 | 4790 | 5700 | 7720 | |
| CV% GM | 54.6 | 21.4 | 32.5 | 50.1 | |
| Cmax (ng/mL) | Mean (SD) | 1870 (732) | 1380 (620) | 1560 (613) | 2020 (1270) |
| GM | 1740 | 1260 | 1440 | 1770 | |
| CV% GM | 44.1 | 51.5 | 47.3 | 56.6 | |
| Tmax (h) | Median (range) | 1.00 (0.500–2.00) | 1.25 (0.500–2.00) | 1.25 (0.500–3.00) | 1.50 (1.00–3.00) |
| GM | N/A | N/A | N/A | N/A | |
| CV% GM | N/A | N/A | N/A | N/A | |
| t½ (h) | Mean (SD) | 12.0 (6.82) | 6.38 (4.88) | 7.62 (8.12) | 6.80 (4.23) |
| GM | 10.4 | 5.37 | 5.77 | 6.08 | |
| CV% GM | 60.3 | 64.2 | 77.0 | 50.1 | |
| CL/F (L/h) | Mean (SD) | 36.1 (19.1) | 42.6 (9.23) | 36.6 (11.4) | 28.2 (11.7) |
| GM | 32.0 | 41.8 | 35.1 | 25.9 | |
| CV% GM | 54.6 | 21.4 | 32.5 | 50.1 | |
| Vz/F (L) | Mean (SD) | 655 (504) | 366 (218) | 340 (227) | 263 (128) |
| GM | 483 | 324 | 292 | 227 | |
| CV% GM | 104.3 | 55.6 | 61.1 | 74.4 |
| Adjusted GMs | GMR (90% CI) | ||||||
|---|---|---|---|---|---|---|---|
| Normal (n = 9) | Mild (n = 6) | Moderate (n = 8) | Severe (n = 6) | Mild/normal | Moderate/normal | Severe/normal | |
| AUCinf (ng × h/mL) | 6240 | 4790 | 5700 | 7720 | 0.767 (0.532–1.11) | 0.914 (0.652–1.28) | 1.24 (0.858–1.78) |
| AUClast (ng × h/mL) | 6190 | 4730 | 5660 | 7710 | 0.764 (0.529–1.10) | 0.915 (0.652–1.28) | 1.24 (0.862–1.80) |
| Cmax (ng/mL) | 1740 | 1260 | 1440 | 1770 | 0.724 (0.476–1.10) | 0.828 (0.563–1.22) | 1.02 (0.669–1.55) |
AUC, area under the plasma concentration–time curve; AUCinf, AUC from time zero to infinity; AUClast, AUC from time zero to last measurable concentration sampling time; CI, confidence interval; CL/F, the apparent total body clearance of drug from the plasma; Cmax, maximum (peak) observed plasma drug concentration after single‐dose administration; CV, coefficient of variation; GM, geometric mean; GMR, geometric mean ratio; SD, standard deviation; t½, elimination half‐life associated with terminal slope (λz) of a semi‐logarithmic concentration–time curve (time); Tmax, time to reach maximum (peak) plasma drug concentration after single‐dose administration (time); Vz/F, apparent volume of distribution during terminal phase.
CV% GM = sqrt (exp [variance for log‐transformed data]‐1) × 100.
Model is a linear model of the log‐transformed PK parameters. Study group was included in the model as a fixed effect. Results were back‐transformed to obtain adjusted GM, GMR and 90% CI.