Nicotine pharmacokinetics
Unadjusted plasma nicotine concentrations that were below the limit of quantitation (BLQ) were set to one-half of the lower limit of quantitation (LLOQ) for the calculation of descriptive statistics. Individual plasma nicotine concentrations were adjusted for baseline nicotine levels (“baseline-adjusted”) and all pharmacokinetic parameters were calculated based on the adjusted concentrations. Baseline adjustment was performed by subtraction of the pre-existing nicotine concentration from each nicotine concentration obtained after test product administration in that period/day for each subject using the following equation:SAS® software (Version 9.4) was used for data presentation and summarisation including descriptive statistics, statistical analyses, summary tables, graphs, and data listings. Descriptive statistics were generated for plasma nicotine concentrations and nicotine pharmacokinetic parameters by study product for all subjects, including sample size (n), arithmetic mean (mean), SD, coefficient of variation (CV%), standard error of the mean (SEM), minimum, median, and maximum at each nominal time-point. In addition, geometric mean, and geometric CV%, are provided for the CA linear mixed-effects model for analysis of variance (ANOVA) was performed on the natural log-transformed pharmacokinetic parameters CA non-parametric analysis (Wilcoxon Signed Rank test) was performed for the comparisons of T