Bioequivalence Study With Lapatinib Powder for Oral Suspension and the Original Tablet Formulation in Cancer Patients

Lapatinib is approved for use in various therapeutic combinations for treating metastatic breast cancers that over-express HER2. To deliver the approved doses, up to six large tablets need to be ingested with the current 250-mg tablets. For ease of ingestion, a powder for oral suspension was developed. This study was an open-label, randomized, adaptive design, two-period crossover bioequivalence study of the powder for suspension relative to the commercial tablet at steady state following once daily dosing for 7 days in patients with advanced cancer. To minimize the number of cancer patients required for a pivotal bioequivalence study (144 in this case), a four-stage adaptive group sequential design with interim analyses after every 36 subjects was implemented to allow for early termination. Bioequivalence for the oral suspension relative to the commercial tablet was demonstrated in both the first (and only) interimanalysis and the final analysis, as the 90% confidence intervals for the treatment comparison ratios for both AUC(0-24) and C-max were contained within the acceptance criteria (0.80, 1.25). Additionally, there was no statistical difference in t(lag) or t(max), suggesting no difference in the absorption rate between treatments. There were no unexpected safety findings during this study.