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

► Electrically heated cigarette smoking system compared to conventional cigarettes. ► Mainstream smoke constituents reduced in the electrically heated cigarette. ► Biomarkers of exposure confirmed reduced exposure in a randomized clinical trial. ► Reductions in exposure to selected smoke constituents approach smoking cessation. ► No clinically relevant adverse effects observed. 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 (M4JM; 4mg tar and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking M4JM, or switch to smoking either the Electrically Heated Cigarette Smoking System menthol cigarette (EHCSS-K6M; 5mg tar and 0.3mg nicotine) or the Lark One menthol cigarette (Lark1M; 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-K6M group (−12.3% to −83.4%). Smaller, but statistically significant reductions (p⩽0.05) occurred in the Lark1M 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.