Simulated clinical PK parameters of sonidegib in the presence and absence of the moderate CYP3A inhibitor, ERY, in cancer patients
| Trial | Treatment | AUC (ng × h/ml) Mean (S.D.) | Cmax (ng/ml) Mean (S.D.) | |
|---|---|---|---|---|
| 0–24 Hours | 0–240 Hours | |||
| 3a | 200 mg sonidegib single dose on day 5 | 1427 (439) | 4752 (2162) | 140 (41.5) |
| 200 mg sonidegib single dose on day 5 + ERY (500 mg q.i.d.) days 1–14 | 1940 (587) | 8087 (3737) | 176 (51.1) | |
| GM ratio (CI) | 1.36 (1.33, 1.39) | 1.70 (1.31, 2.32) | 1.26 (1.23, 1.28) | |
| 3b | 200 mg sonidegib q.d. days 1–120 | 8279 (3855) | —a | 439 (176) |
| 200 mg sonidegib q.d. days 1–120 + ERY (500 mg q.i.d.) days 1–120 | 23,457 (11,611) | — | 1091 (497) | |
| GM ratio (CI) | 2.79 (1.76, 4.61) | — | 2.43 (1.63, 3.94) | |
| 3c | 200 mg sonidegib q.d. days 1–133 | 8297 (3869) | — | 440 (177) |
| 200 mg sonidegib q.d. days 1–133 + ERY (500 mg q.i.d.) days 120–133 (14 days) | 14,600 (6329) | — | 718 (280) | |
| GM ratio (CI) | 1.79 (1.71, 1.86) | — | 1.64 (1.58, 1.70) | |
CI, confidence interval (90%).
↵a Not simulated.