Pharmacokinetic Analyses
All subjects who received both study treatments, completed scheduled
posttreatment PK evaluations, and were protocol compliant were included
in the PK analysis set. Subjects who vomited within twice the median
Tmax were excluded from the primary analysis.
Paclitaxel plasma concentrations were normalized to
615mg/m2 for oPac+E and 80 mg/m2 for
IV paclitaxel. Pharmacokinetic and statistical analyses were based on
normalized plasma concentrations. Plasma concentrations for paclitaxel
were analysed to determine the following PK parameters by
noncompartmental analysis using plasma concentration time data for oral
and IV paclitaxel: AUC0-∞ (primary endpoint) as well as
Cmax, AUC0-t, Tmax, and
t½ (secondary endpoints).
The equivalence of the extent of exposure was determined by comparing
the AUC0-∞ of the selected dose of oral paclitaxel (as
oPac+E) (administered over 3 consecutive days) to the
AUC0-∞ of IV paclitaxel.
The primary PK parameters were compared between IV paclitaxel
(reference) and oral paclitaxel (test) formulations. Analysis of
variance (ANOVA) was performed (α=0.05) on the untransformed and log10
transformed PK parameters Cmax, AUC0-t,
and AUC0-∞ for paclitaxel. The ANOVA model included
sequence, subjects nested within the sequence, period, and formulation
as factors. The significance of the sequence effect was tested using the
subjects nested within the sequence as the error term. Two-sided 90%
CIs for the log transformed ratio of test/reference of the least squares
means obtained from the ANOVA for Cmax,
AUC0-t, and AUC0-∞ were estimated.
Equivalence was to be concluded if the 90% CI of the ratio (oral
paclitaxel 615mg/m2 over 3 consecutive days
[oPac+E] / 80 mg/m2 IV paclitaxel) of the least
square means from the ANOVA of the log-transformed
AUC0-∞ was within the 80% to 125% acceptance range.