TABLE 6

Simulated clinical PK parameters of sonidegib in the presence and absence of the strong CYP3A inducer, RIF, in cancer patients

TrialTreatmentAUC (ng × h/ml) Mean (S.D.)Cmax (ng/ml)
Mean (S.D.)
0–24 Hours0–240 Hours
2a800 mg sonidegib single dose on day 52856 (879)9510 (4328)280 (83.1)
800 mg sonidegib single dose on day 5 + RIF (600 mg q.d.) days 1–141054 (528)2246 (1481)136 (62.6)
GM ratio (CI)0.34 (0.31, 0.37)0.21 (0.19, 0.23)0.45 (0.43, 0.49)
200 mg sonidegib single dose on day 51428 (440)4755 (2164)140 (41.5)
200 mg sonidegib single dose on day 5 + RIF (600 mg q.d.) days 1–14532 (285)1133 (795)68.7 (34.0)
GM ratio (CI)0.34 (0.32, 0.37)0.21 (0.19, 0.23)0.46 (0.43, 0.49)
2b200 mg sonidegib q.d. days 1–1208288 (3859)a439 (176)
200 mg sonidegib q.d. days 1–120 + RIF (600 mg q.d.) days 1–1201124 (886)94.4 (59.0)
GM ratio (CI)0.12 (0.11, 0.13)0.20 (0.18, 0.22)
2c200 mg sonidegib q.d. days 1–1338303 (3872)440 (177)
200 mg sonidegib q.d. days 1–133 + RIF (600 mg q.d.) days 120–133 (14 days)1858 (1364)126 (73.6)
GM ratio (CI)0.20 (0.18, 0.22)0.27 (0.24, 0.29)
  • CI, confidence interval (90%).

  • a Not simulated.