TABLE 5

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

TrialTreatmentAUC (ng × h/ml) Mean (S.D.)Cmax (ng/ml) Mean (S.D.)
0–24 Hours0–240 Hours
1a800 mg sonidegib single dose on day 52855 (879)9504 (4324)280 (83)
800 mg sonidegib single dose on day 5 + KTZ (200 mg b.i.d.) days 1–144036 (1186)17,526 (7819)361 (105)
GM ratio (CI)1.42 (1.39, 1.45)1.85 (1.78, 1.93)1.29 (1.27, 1.32)
200 mg sonidegib single dose on day 51428 (440)4754 (2163)140 (41.5)
200 mg sonidegib single dose on day 5 + KTZ (200 mg b.i.d.) days 1–142018 (593)8763 (3910)181 (52.4)
GM ratio (CI)1.42 (1.39, 1.45)1.85 (1.78, 1.93)1.29 (1.27, 1.32)
1b200 mg sonidegib q.d. days 1–1208285 (3857)a439 (176)
200 mg sonidegib q.d. days 1–120 + KTZ (200 mg b.i.d.) days 1–12028,836 (12,772)1318 (547)
GM ratio (CI)3.53 (3.31, 3.76)2.99 (2.83, 3.16)
1c200 mg sonidegib q.d. days 1–1338301 (3871)440 (177)
200 mg sonidegib q.d. days 1–133 + KTZ (200 mg b.i.d.) days 120–133 (14 days)16,189 (6628)786 (293)
GM ratio (CI)2.01 (1.92, 2.11)1.81 (1.74, 1.88)
1d200 mg sonidegib q.o.d. days 1–1338293 (3867)b280 (101)
200 mg sonidegib q.o.d. days 1–133 + KTZ (200 mg b.i.d.) days 120–133 (14 days)15,522 (6310)b450 (153)
GM ratio (CI)1.93 (1.84, 2.02)1.62 (1.57, 1.67)
  • CI, confidence interval (90%).

  • a Not simulated.

  • b AUC0–48h.