Data Analysis

For all biomarkers of exposure and all three study arms, means and standard deviations were calculated for baseline (average of D0 and D –1), end of exposure (average of D4 and D5), and for the change from baseline to end of exposure, along with 95% confidence intervals. Differences of the means between the CHTP and CC groups and their 95% confidence intervals were calculated. To demonstrate reduced levels of the primary biomarkers of exposure (COHb, S-PMA, and total NNAL) in the CHTP compared with the CC arm at the end of the exposure, we conducted an analysis of covariance comparing differences between the two arms at an unadjusted alpha level of 5% each. Covariates considered in this analysis were sex, usual daily CC consumption and the baseline level of the analyzed biomarker of exposure. In addition, terms for interactions between study arm and sex, and between study arm and usual daily CC consumption were included, whenever the corresponding interaction test resulted in a P value ≤ 10%. Data were analyzed using SAS V8.2 (SAS Institute Inc, Cary, NC).