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

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 (AUC(0–t)), area under the plasma concentration–time curve from time 0 to infinity (AUC(0–∞)), and peak (maximum) plasma drug concentration (C(max)) 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 C(max) (t(max)) and an ~ 34.5% reduction in C(max). 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.