TABLE 8

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

TrialTreatmentAUC (ng × h/ml) Mean (S.D.)Cmax (ng/ml) Mean (S.D.)
0–24 Hours0–240 Hours
4a200 mg sonidegib single dose on day 51470 (510)4970 (2142)151 (53.5)
200 mg sonidegib single dose on day 5 + EFV (600 mg q.d.) days 1–141058 (398)2738 (1361)124 (46.2)
GM ratio (CI)0.71 (0.69,0.74)0.53 (0.50, 0.57)0.81 (0.79, 0.83)
4b200 mg sonidegib q.d. days 1–1209238 (5229)a487 (243)
200 mg sonidegib q.d. days 1–120 + EFV (600 mg q.d.) days 1–1203380 (2126)227 (114)
GM ratio (CI)0.35 (0.33,0.38)0.46 (0.44,0.49)
4c200 mg sonidegib q.d. days 1–1339256 (5251)488 (244)
200 mg sonidegib q.d. days 1–133 + EFV (600 mg q.d.) days 120–133 (14 days)4585 (3107)279 (155)
GM ratio (CI)0.47 (0.44, 0.50)0.56 (0.53,0.59)
  • CI, confidence interval (90%).

  • a Not simulated.