A study to examine changes in exposure to cigarette smoke chemicals when a smoker switches to using a tobacco heating product

INTERVENTION: Participants will be randomised either to: 1. Remain smoking a conventional (control) cigarette (mentholated or non‐mentholated) for 5 days 2. Switch to using a developmental tobacco heating product (mentholated or non‐mentholated) for 5 days 3. Switch to using a commercially‐available tobacco heating product for 5 days 4. Cease the use of any tobacco products for 5 days After entering the clinic, subjects will smoke regular cigarettes ad libitum and up to a maximum amount of 120% of their usual daily cigarette consumption, for a baseline period of 2 days. After this period and according to the randomisation, subjects will either remain smoking for the next 5 days or will switch to using a tobacco heating product or refrain from using any tobacco products, also for 5 days. After this period, subjects in all the tobacco‐use groups will remain in the clinic for a further day for a single‐use nicotine pharmacokinetic sampling period. After the study, subjects will be followed‐up after a period of 5‐7 days. CONDITION: Cigarette smoking ; Mental and Behavioural Disorders ; Mental and behavioural disorders due to use of tobacco PRIMARY OUTCOME: 1. Within‐group changes in urinary biomarkers of exposure to cigarette smoke toxicants (TNeq, total NNAL, total NNN, 3‐HPMA, HMPMA, S‐PMA, MHBMA, CEMA, 4‐ABP, o‐Tol, 2‐AN, 1‐OHP, HEMA, AAMA and GAMA), measured in daily 24h urine collections (2 baseline days and 5 product use days); 2. Within‐group changes in exhaled breath CO (measured daily in exhaled breath using a CO meter), urinary 8‐Epi‐PGF2a Type III (measured daily from a urine sample) and white blood cell count (performed daily on a sample of venous blood) SECONDARY OUTCOME: 1. Between‐group differences in urinary biomarkers of exposure to cigarette smoke toxicants (TNeq, total NNAL, total NNN, 3‐HPMA, HMPMA, S‐PMA, MHBMA, CEMA, 4‐ABP, o‐Tol, 2‐AN, 1‐OHP, HEMA, AAMA and GAMA), measured in daily 24h urine collections (2 baseline days and 5 product use days); 2. Between‐group differences in exhaled breath CO (measured daily in exhaled breath using a CO meter), urinary 8‐Epi‐PGF2a Type III (measured daily from a urine sample) and white blood cell count (performed daily on a sample of venous blood); 3. Plasma nicotine pharmacokinetic parameters (Tmax, Cmax and AUC0‐tlast), measured in venous blood samples taken at ‐5, 1, 3, 4, 5, 6, 7, 10, 15, 30, 60, 120, and 240 minutes relative to the first puff on a single cigarette/THP consumable; 4. Subjects' satisfaction with the study products, assessed using a single‐item questionnaire at the end of all study procedures; 5. Safety profile, assessed at the end of the study period by examining adverse event record and also by vital signs, physical examination, ECG, lung function test, blood and urine tests and a pregnancy test (female subjects only) INCLUSION CRITERIA: 1. Subjects will be males or females of Japanese origin and between 23 and 55 years of age, inclusive 2. Subjects will have a body mass index (BMI) between 17.6 and 32.0 kg/m2, inclusive; a body weight exceeding 50 kg (males) or 40 kg (females) 3. Subjects will be in good health, as judged by the PI or designee based on medical history, physical examination, vital signs assessment, 12‐lead ECG, clinical laboratory evaluations and lung function tests 4. Subjects will have given their written informed consent to participate in the study and will have agreed to abide by the study restrictions 5. Subjects must demonstrate the ability to comprehend the Informed Consent Form (ICF), be able to communicate well with the PI or their appropriately qualified designee, understand and comply with the requirements of the study, and be judged suitable for the study in the opinion of the PI or their appropriately qualified designee 6. Subjects will be willing to refr