Uptake of nicotine following a single use of "Heat Not Burn" (HNB) 1.2 and a cigarette

INTERVENTION: Potential subjects will undergo screening procedures to ensure they satisfy the inclusion and exclusion criteria of the study. During Screening, potential subjects will practice with the HNB 1.2 product under the supervision of the clinic staff to ensure that they would be willing and able to use it as required during study conduct. Subjects will check‐in to the clinic and will be allowed to smoke their usual brand cigarette products ad libitum until 23:00. Following check‐in procedures, a sample will be collected for trans‐3’‐hydroxycotinine cotinine ratio determination. Participants will then abstain from nicotine and tobacco product use for 24 hours (wash‐out period). Days 1 and 2 will be product administration days. Each product administration day will include a controlled administration of either the HNB 1.2 product or the reference cigarette according to the randomisation schedule. The administration of the HNB 1.2 product will consist of 10 puffs for 3 minutes, at approximately 20‐second intervals, or smoking one reference cigarette, 10 puffs for 3 minutes, at approximately 20‐second intervals. The number of puffs from the HNB 1.2 and the reference cigarette will be documented by the clinical staff. The MLE from the HNB 1.2 will be assessed from the change in product weight from before to after use. Used cigarette butts will be collected and saved to assess MLE nicotine from the filter tips. Subject health status will be evaluated on Day 2 prior to discharge. Serial blood samples will be collected at approximately 10 minutes prior to and at 2, 3, 4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60, 90, and 120 minutes following the start of the controlled product administration to determine plasma nicotine concentrations. Nicotine PK parameters will be determined using a non‐compartmental approach. Parameters will include Cmax, tmax, AUClast, AUC0‐8, t1/2, F(AUC0 8), tlast, Clast, ?z, number of points, ?z_lower, ?z_upper, R2adj, and AUCext%. Baseline adjustments may CONDITION: Nicotine uptake ; Respiratory ; Nicotine uptake PRIMARY OUTCOME: Uptake of nicotine from the HNB 2.1 product as measured using plasma nicotine concentrations obtained from blood samples taken at 2, 3 ,4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60 and 90 minutes following use of the HNB 1.2 product. INCLUSION CRITERIA: 1. Aged between 21 to 50 years of age 2. Good general health 3. Smoker for at least 12 months prior to check‐in and currently smokes an average of 10 or more manufactured cigarettes per day (no restriction on brand‐style, king size [ 83 – 85 mm] and 100s [ 98 – 100 mm] only) 4. Positive urine cotinine at screening (> 200 ng/mL) at screening 5. Female subjects must be non‐pregnant and non‐lactating 5. Pre‐menopausal female subjects must be surgically sterile, use an investigator‐approved method of birth control, or agree to be sexually abstinent from 14 days prior to check‐in through the end of the study SECONDARY OUTCOME: 1. Nicotine pharmacokinetic parameters (e.g. maximum nicotine concentration (Cmax) and time to Cmax (tmax)) measured using plasma nicotine concentrations obtained from blood samples taken at 2, 3 ,4, 5, 6, 7, 8, 10, 15, 20, 25, 30, 45, 60 and 90 minutes following use of the HNB 1.2 product; 2. Volunteer mouth level exposure (MLE) to nicotine during use of the HNB 2.1 product, as measured by the difference in weight of HNB 2.1 product + its associated pod insert before and after product use; 3. Volunteer mouth level exposure (MLE) to nicotine during use of the CC1 product, as measured by assessing the amount of nicotine present in the product filter after product use; 4. Volunteer inhalation to non‐inhalation ratios during use of the HNB 2.1 product as measured by vidual analogue scare (VAS) questionnaire following use of the HNB 1.2 product