Cigarette smoking Mental and Behavioural Disorders Mental and behavioural disorders due to use of tobacco
Conditions
Interventions
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 develop
Sponsors
British American Tobacco (Investments) Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 refrain from consuming alcohol within 72 hours prior to Screening and Admission 7. Subjects will be willing to refrain from consuming cruciferous vegetables, and grilled, fried or barbequed food, and avoid being in the presence of the cooking of cruciferous vegetables, and grilled, fried or barbequed food for 48 hours prior to Admission. Subjects will also be willing to avoid food containing poppy seeds for 3 days before both screening and Admission 8. Subjects will be regular smokers of factory-made cigarettes whose chosen brand is within the ISO tar bands 6 mg to 8 mg 9. Subjects will have smoked their chosen brand for a minimum of 6 months and will have smoked for at least 3 consecutive years prior to Screening 10. Subjects will typically smoke at least 10 and a maximum of 30 cigarettes per day and must have a urine cotinine level >200 ng/mL and an exhaled breath CO level >10 ppm at Screening. 11. Subjects will be willing to use the study products (comparator cigarette or THP product) and smoke only the products provided to them during clinical confinement, or to abstain from smoking if assigned to the cessation arm
Exclusion criteria
Exclusion criteria: 1. Male subjects who do not agree, or whose partners of childbearing potential do not agree, to use a barrier method of contraception (i.e., a condom with spermicide) in addition to a second highly effective method of contraception used by their female partners or to refrain from donating sperm from Admission (Day -1) until the end of the safety Follow-up period (5-7 days after Discharge) 2. Female subjects of childbearing potential who do not agree to use a highly effective method of birth control in conjunction with male barrier method contraception (i.e. a condom with spermicide) from the time of signing the ICF until the end of the safety Follow-up period (5-7 days after Discharge) 3. Female subjects who are pregnant or breastfeeding. This will be confirmed at Screening and Admission. Any female subject who becomes pregnant during this study will be withdrawn 4. Subjects who have donated =400 mL of blood within 90 days prior to Admission; plasma in the 7 days prior to Admission; or platelets in the 6 weeks prior to Admission 5. Subjects who have an acute illness (e.g. upper respiratory tract infection, viral infection, etc.) requiring treatment within 4 weeks prior to Admission 6. Subjects who have regularly used any nicotine or tobacco product other than commercially manufactured filter cigarettes within 14 days of Screening 7. Subjects who are self-reported non-inhalers (smokers who draw smoke from the cigarette into the mouth and throat but who do not inhale). Subjects who are observed as non-inhalers at Admission by the clinic staff will be excluded 8. Subjects who, prior to enrolment, are planning to quit smoking in the next 12 months. All subjects will be informed that they are free to quit smoking and withdraw from the study at any time. Any subject who decides to quit smoking will be directed to appropriate stop smoking services 9. Subjects who have a significant history of alcoholism or drug/chemical abuse within 24 months prior to Screening, as determined by the PI 10. Subjects who have a positive urine drugs of abuse screen at Screening or Admission; or a positive alcohol breath test at Screening or Admission 11. Subjects who have serum hepatitis; are carriers of the hepatitis B surface antigen (HBsAg); are carriers of the hepatitis C antibody; have a positive result for the test for human immunodeficiency virus (HIV) antibodies; or have syphilis 12. Subjects who have used prescription or over-the-counter (OTC) bronchodilator medication (e.g. inhaled or oral ß-adrenergic agonists) to treat a chronic condition within the 12 months prior to Admission 13. Subjects who have received any medications or substances (other than tobacco) which interfere with the cyclooxygenase pathway (e.g. anti-inflammatory drugs including aspirin and ibuprofen) within 14 days prior to Admission; or are known to be strong inducers or inhibitors of cytochrome P450 (CYP) enzymes within 14 days or 5 half-lives of the drug (whichever is longer) prior to Admission 14. Subjects who perform strenuous physical activity (exceeding the subject’s normal activity levels) within 7 days prior to Screening or Admission 15. Subjects who are unable to communicate effectively with the PI/study staff (i.e. language problem, poo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Japan
Outcome results
None listed