Purpose: Ridaforolimus, a potent inhibitor of the mammalian target of rapamycin (mTOR), is under development for the treatment for solid tumors. This open-label, randomized, 3-period crossover study investigated the effect of food on the pharmacokinetics of ridaforolimus 40 mg as well as safety and tolerability of the study medication.
Methods: Ridaforolimus was administered to 18 healthy, male subjects (mean age 36.4 years) in the fasted state, following ingestion of a light breakfast, and following a high-fat breakfast. Whole blood samples were collected from each subject pre-dose and 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, and 168 h post-dose.
Results: The geometric mean (95 % confidence interval, CI) fasted blood area under the curve (AUC(0-∞)) and maximum concentration (C(max)) were 1940 (1510, 2500) ng h/mL and 116 (87, 156) ng/mL, respectively, and median time to C(max) (T(max)) and average apparent terminal half-life (t(1/2)) were 6.0 and 64.5 h, respectively. Both T(max) and t(1/2) were similar in the fasted and fed states. With a light breakfast, the geometric mean intra-individual ratios (GMRs) for AUC(0-∞) and C(max) (fed/fasted) and 90 % CIs were 1.06 (0.85, 1.32) and 1.15 (0.83, 1.60); following a high-fat breakfast, the AUC(0-∞) and C(max) GMRs (90 % CI) were 1.46 (1.18, 1.81) and 1.12 (0.81, 1.53), respectively.
Conclusions: Increases in ridaforolimus exposure following both the light and high-fat breakfasts were not considered to be clinically meaningful. Ridaforolimus was generally well tolerated, and there were no discontinuations due to drug-related AEs. Ridaforolimus should be given without regard to food.