Statistical analysis
Pharmacokinetic parameters of Org 48775-0, Cmax,
tmax, AUC∞, t½ and CL/F
were determined based on the individual plasma concentration-time data,
using ANOVA software. Descriptive pharmacokinetic statistical analysis
was only performed if at least 2/3 of the concentrations by time point
were greater than or equal to the LLOQ.
The ex vivo inhibition of TNFα release after study drug
administration was analyzed per cohort, with a mixed model analysis of
variance (using SAS PROC MIXED). Data were log-transformed before
analysis and treatment effect was reported as active versus placebo, as
fasted versus fed for the food interaction study, and as male versus
female for the gender effect study. The in vitro inhibition of
TNFα release was modeled with an inhibitory effect sigmoid Emax model
(using SAS PROC LIN; WinNonlin Nonlinear Estimation, software version
5.0, Pharsight, Mountain View, California, USA).Results