TABLE 4

Observed and simulated clinical PK parameters of sonidegib in healthy subjects and cancer patients

TreatmentPopulation (Study)StatisticsAUC0–lasta (ng × h/ml)Cmax (ng/ml)
ObservedSimulatedObservedSimulated
200 mg sonidegib single doseHealthy subjects (A2114)n1010012100
Mean (S.D.)3327 (1822)4596 (2178) PE = +38%104 (45)119 (36.8) PE = +14%
GM2481410487.0113
Cancer patients (X2101)n61006100
Mean (S.D.)3673 (2133)4026 (1759) PE = +10%160 (115)140 (41.6) PE = −13%
GMb3695134
800 mg sonidegib single doseHealthy subjects (A2114)n1110013100
Mean (S.D.)12,087 (7888)9192 (4355) PE = −24%258 (155)238 (73.6) PE = −8%
GM10,3488208216227
Healthy subjects (A2110)n61006100
Mean (S.D.)8680 (2510)9192 (4355) PE = +6%154 (33)238 (73.6) PE = +55%
GM83708208151227
Healthy subjects (A2108, control arm)n1610016100
Mean (S.D.)6080 (2530)6431 (2993) PE = +6%246 (158)238 (73.4) PE = −3%
GM56205816212227
Cancer patients (X2101)n2510025100
Mean (S.D.)7867 (6950)8052 (3517) PE = +2%429 (381)280 (83.2) PE = −35%
GM7390268
200 mg sonidegib multiple doseCancer patients (X2101)n51005100
Mean (S.D.)5916 (3886)5788 (2690) PE = −2%269 (163)333 (130) PE = +24%
GM5243310
800 mg sonidegib multiple doseCancer patients (X2101)n2010020100
Mean (S.D.)12,781 (6351)11,575 (5380) PE = −9%840666 (259) PE = −21%
GM10,485621
  • n, number of subjects with nonmissing values; PE, prediction error % = [(predicted value − observed value)/observed value] × 100.

  • a AUClast for A2114 = 0–2016 hours; X2101 = 0–168 hours for the single dose and 0–24 hours for the multiple dose; A2110 = 0–2016 hours; A2108 = 0–240 hours.

  • b Not determined.