Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 6: 6-Day randomized clinical trial of a menthol cigarette in Japan.

A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine, and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4J(M); 4 mg tar and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking M4J(M), or switch to smoking either the Electrically Heated Cigarette Smoking System menthol cigarette (EHCSS-K6(M); 5mg tar and 0.3mg nicotine) or the Lark One menthol cigarette (Lark1(M); 1mg tar and 0.1mg nicotine), or to no-smoking. The mean decreases from baseline to Day 5/6 were statistically significant (p ≤ 0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary endpoint (carbon monoxide) and urinary excretion of mutagenic material in the EHCSS-K6(M) group (-12.3% to -83.4%). Smaller, but statistically significant reductions (p ≤ 0.05) occurred in the Lark1(M) group (-3.3% to -35.2%), with the exception of urinary mutagens. The largest mean reductions (all p ≤ 0.05) in exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in the no-smoking group (-1.4% to -93.6%). Serum CC16, an indicator of lung epithelial injury, was not significantly different between groups.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland.

This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 4: Eight-day randomized clinical trial in Korea.

A randomized, controlled, open-label parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 72 male and female Korean subjects smoking Lark One cigarettes (1.0mg tar, 0.1mg nicotine, and 1.5mg CO) at baseline. Subjects were randomized to continue smoking Lark One cigarettes, or switch to an Electrically Heated Cigarette Smoking System (EHCSS) and EHCSS-K3 cigarette (3mg tar, 0.2mg nicotine, and 0.6 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (all p<0.05) for 10 of 12 HPHC in mainstream cigarette smoke including CO (the primary objective) in the EHCSS-K3 group (range: -1.5% to -74.2%). Exposure to the other determined HPHC was not significantly different. In the Lark One group, the mean exposure to 6 of 12 HPHC in cigarette smoke was significantly (all p<0.05) decreased; however, exposure to CO was significantly increased. The largest mean reductions in biomarkers of exposure to HPHC occurred in smokers who switched to no-smoking (-3.4% to -98.9%). The mean excretion of mutagenic material was significantly decreased (p<0.05) in the EHCSS-K3 and no-smoking groups (-31.8% and -45.3%, respectively), and increased in the Lark One group (+31.5%).