TABLE 1.
PK parameters for asciminib in the inhibitor/inducer study
| Parameters | Asciminib (n = 18) | Asciminib + itraconazole (oral solution) (n = 17) | Asciminib (n = 10) | Asciminib + itraconazole (capsule) (n = 10) | Asciminib (n = 14) | Asciminib + clarithromycin (n = 14) | Asciminib (n = 18) | Asciminib + rifampicin (n = 17) | Asciminib (n = 19) | Asciminib + quinidine (n = 18) |
|---|---|---|---|---|---|---|---|---|---|---|
| Cohort 1 | Cohort 6 | Cohort 5 | Cohort 3 | Cohort 2 | ||||||
| AUCinf (ng*h/ml), G mean (GCV%) | 7000 (25.1) | 4200 (32.8) | 5630 (39.8) | 5830 (45.4) | 5740 (34.0) | 7820 (31.0) | 5630 (31.3) | 4740 (24.2) | 6750 (30.0) | 5800 (32.7) |
| AUClast (ng*h/ml), G mean (GCV%) | 6950 (25.2) | 4090 (33.4) | 5590 (40.2) | 5780 (46.0) | 5670 (34.4) | 7750 (30.4) | 5400 (30.6) | 4670 (24.3) | 6700 (30.0) | 5550 (29.9) |
| Cmax (ng/ml), G mean (GCV%) | 679 (27.4) | 338 (35.2) | 554 (42.1) | 578 (40.4) | 537 (35.6) | 642 (30.8) | 559 (38.8) | 599 (25.1) | 618 (35.8) | 539 (32.5) |
| Tmax (h), median (range) | 2.00 (1.00–4.02) | 2.00 (0.97–3.98) | 2.01 (1.93–3.00) | 2.03 (1.98–3.00) | 2.02 (1.00–3.00) | 2.02 (1.98–3.03) | 2.00 (1.98–4.00) | 2.00 (0.98–3.00) | 2.00 (1.00–4.00) | 2.00 (0.98–3.98) |
| t½ (h), G mean (GCV%) | 12.6 (18.8) | 13.9 (41.1) | 11.5 (17.6) | 10.6 (18.3) | 12.5 (14.9) | 14.5 (18.0) | 10.5 (15.1) | 8.35 (9.5) | 12.4 (17.4) | 11.3 (14.3) |
| CL/F (L/h), G mean (GCV%) | 5.71 (25.1) | 9.53 (32.8) | 7.11 (39.8) | 6.86 (45.4) | 6.97 (34.0) | 5.11 (31.0) | 7.11 (31.3) | 8.43 (24.2) | 5.92 (30.0) | 6.90 (32.7) |
Abbreviations: AUC, area under the curve; AUCinf, AUC from zero to infinity; AUClast, AUC from zero to the last quantifiable concentration; CL/F, apparent plasma clearance; Cmax, maximum concentration of drug in plasma; GCV%, geometric coefficient of variation; G mean, geometric mean; PK, pharmacokinetic; t 1/2, terminal half‐life; Tmax, time to reach maximum concentration of drug in plasma.