A Phase 1 Study to Assess the Relative Bioavailability of Brigatinib Administered as an Oral Solution Versus an...

Brigatinib is an ALK tyrosine kinase inhibitor approved for the treatment of adults with ALK+ non-small cell lung cancer. The commercial formulation of brigatinib is an immediate-release (IR) tablet; however, an oral solution was developed for use in pediatric studies for patients unable to swallow solid oral dosage forms. This randomized, two-period, two-sequence crossover study assessed the relative bioavailability of the oral solution versus the IR tablet in healthy adults. Twelve participants received a single 90-mg brigatinib dose as the oral solution or IR tablet on Day 1 of the first study period, followed by the alternate formulation on Day 1 of the second study period. Brigatinib pharmacokinetic parameters were similar following administration of the oral solution and IR tablet. The geometric least-square mean ratios (oral solution vs IR tablet) for C_max (0.92), AUC_last (0.96), and AUC_inf (0.96) were close to 1.00 with 90% confidence intervals within the bioequivalence range of 0.80-1.25 (C_max, 0.87-0.98; AUC_last, 0.88-1.04; AUC_inf, 0.89-1.03). Treatment-emergent adverse events were reported in three participants (25%), with the most frequent being cough (17%). These results indicate that the oral solution and IR tablet can be used interchangeably without dose adjustment in pediatric studies.