A Phase I, open-label, randomized, crossover study in healthy subjects to evaluate the bioavailability of, and the food effect on, a pomalidomide oral liquid suspension.
Yan Li, Liangang Liu, Lian Huang, Xiaomin Wang, Matthew Hoffmann, Josephine Reyes, Maria Palmisano, Simon Zhou
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引用次数: 3
Abstract
Objective: The aim of this study was to evaluate the bioavailability of a pomalidomide oral liquid suspension relative to the commercial capsule formulation and to assess the food effect on the pomalidomide oral liquid suspension when administered as a single 4 mg dose.
Methods: This was an open-label, randomized, three-period, two-sequence crossover study in healthy subjects consisting of a screening phase, a baseline assessment phase, a treatment phase with three periods, and a follow-up phone call phase. Blood samples for pharmacokinetics (PK) assessment were collected up to 48 h postdose during each treatment period. Safety was evaluated throughout the study.
Results: Pomalidomide exposures were comparable in healthy subjects administered with a single oral 4 mg dose as the reference capsule or as the test liquid suspension formulations, demonstrated as the 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve calculated from time 0 to the last measurable concentration at time t (AUC0-t), area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞), and peak (maximum) plasma drug concentration (Cmax) were completely contained within the bioequivalence range of 80-125%. Administration of the pomalidomide liquid suspension with a high fat meal resulted in a 3.0 h delay in pomalidomide time to Cmax (tmax) and an ~ 34.5% reduction in Cmax. However, the AUCs were comparable after dose administration with and without food.
Conclusion: A single oral dose of 4 mg of liquid suspension was bioequivalent to a single oral dose of 4 mg of capsule formulation. There was no clinically relevant impact of food on pomalidomide liquid suspension. Single oral doses of 4 mg pomalidomide were safe and well tolerated when administered as a liquid suspension under fed and fasted conditions or as a capsule under fasted conditions.
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