A Controlled, Randomised, Open-label, 3-arm Parallel Single-centre Confinement Study to Investigate Exposure to Selected Smoke Constituents in Smokers Switching From Conventional Cigarettes to SMAR Cigarettes for 5 Days

Distillation based smoking article (SMAR cigarette)

conventional cigarette

smoking cessation

To demonstrate a reduction in the three primary biomarkers of exposure: Carboxyhaemoglobin concentration in blood, Urinary excretion of S-phenylmercapturic acid and urinary excretion of NNAL and NNAL-glucuronides (total NNAL)

To assess the mutagenicity potential in urine at the end of the study in the three study arms

To explore changes from baseline COHb, S-PMA, and total NNAL in the three study arms in the course of the study

To explore changes from baseline in the three study arms with regard to urinary excretion of biomarkers of exposure to several other smoke constituents.

To assess urinary excretion of nicotine and its five major nicotine metabolites in the three study arms

To assess nicotine and cotinine concentrations in plasma in the three study arms To compare levels of all biomarkers of exposure in the SMAR arm to those in the smoking cessation (SC) arm

To monitor blood pressure, pulse rate, electrocardiogram, clinical laboratory parameters (standard clinical biochemistry, standard haematology and urine analysis), and adverse events

To investigate craving and withdrawal symptoms as well as pulmonary symptoms in all three study arms by means of questionnaires

To investigate change in cytochrome P450 1A2 (CYP1A2) activity from D0 to D5 in the three study arms

To assess and compare human smoking topography (HST) in smokers before and after switching to SMAR