Sample Size Rationale
It was planned to enrol an initial cohort of up to 6 patients with an oPac+E dosing regimen consisting of oral encequidar 15 mg plus an oral paclitaxel dose of 615mg/m2 divided over 3 consecutive days taken in once daily doses. An interim analysis of pharmacokinetic (PK) data was conducted to determine the intrasubject variability and geometric mean ratio (GMR) for AUC0-∞. If it appeared likely that the selected regimen could meet the criteria for BE based on AUC0-∞, additional subjects would be enrolled in Stage 2 at this dose. Based on this pre-planned interim analysis, an additional 34 evaluable subjects were enrolled into Stage 2. A total sample size of 40 evaluable subjects was projected to provide 90% power for the 90% CI of the geometric mean ratio for AUC0-∞ to fall in the range of 80% to 125%.