Development of Biomarkers of Effect From Chronic Tobacco Usage

Exclusion Criteria

• •Subjects who met any of the following criteria will be excluded from the study:
• •1. Met cohort specific exclusions as follows:
• •1. Smokers: For three years prior to the study through Day -1, the use of any tobacco- or nicotine containing product or device other than FF or FFLT tobacco-burning cigarettes, including tobacco-heating cigarettes, e cigarettes, beedis, chewing tobacco, dry snuff, moist snuff, snus, or any nicotine replacement therapy (NRT) (e.g., patch, gum, lozenge, inhaler, spray, etc.). NOTE: Subjects who have smoked \< 6 cigars in the past 12 months prior to screening would NOT have been excluded. Subjects who received short-term administration of a NRT as a temporary bridging treatment would NOT have been excluded.
• •2. Moist Snuff Consumers: For three years prior to the study through Day -1, the use of any other tobacco- or nicotine-containing product or device other than moist snuff, including tobacco-burning cigarettes, tobacco-heating cigarettes, e-cigarettes, beedis, cigars, pipes, chewing tobacco, snus, dry snuff, or any NRT (e.g., patch, gum, lozenge, inhaler, spray, etc.). NOTE: Subjects who received short-term administration of a NRT as a temporary bridging treatment would NOT have been excluded.
• •3. Non Tobacco Consumers: For five years prior to the study through Day -1, the use of any kind of tobacco products or the use of any non-tobacco nicotine-containing products (NRTs) or devices (e.g., e-cigarettes).
• •2. Subjects who were tobacco consumers: expressed an interest in quitting smoking or using moist snuff (defined as planning a quit attempt within a month of screening).
• •3. Subjects who were MSC users or non tobacco consumers: an ECO \> 5 ppm at screening or study check-in (ECO of 6 to 10 ppm may not have been excluded based on joint review by the Sponsor and Investigator).
• •4. Subjects who were smokers: an ECO \< 10 ppm at screening or study check-in (ECO of 2 to 9 ppm may not have been excluded based on joint review by the Sponsor and Investigator).
• •5. Any chronic illness that, in the opinion of the Investigator, is unstable.
• •6. A temperature above 99.5° F.
• •7. Poor peripheral venous access.
• •8. Clinically uncontrolled hypertension (\>/= 180 mmHg systolic or \>/= 100 mmHg diastolic blood pressure).
• •9. Diabetes mellitus (either insulin-dependent or non-insulin dependent).
• •10. Blood sugar levels \> 130 mg/dL after the minimum 8 hour fast requested at screening.
• •11. Peak flow ≤ 70% of predicted average peak expiratory flow (PEF) for age and height.
• •12. Clinical manifestations of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders.
• •13. History or presence of an abnormal electrocardiogram (ECG), which, in the Investigator's opinion, is clinically significant.
• •14. History of alcohol abuse or illicit drug use within one year prior to study entry. NOTE: Subjects who self-reported drinking less than or equal to 14 servings of alcoholic beverages per week (1 serving = 12 ounces of beer, 6 ounces of wine, or 1 ounce of liquor) were NOT excluded.
• •15. Presence of an acute infection, with or without antibiotic treatment.
• •16. Any history of abnormal bleeding or clotting disorder, or an individual taking any anticoagulants.
• •17. Any history of clotting disorder from Factor V who is taking anticoagulants.
• •18. Cancer that has been treated successfully, but less than 5 years since completion of treatment, other than skin cancer (exclusionary of melanoma).
• •19. Squamous or basal cell cancers of the skin that had NOT been completely removed.
• •20. History of leukemia or lymphoma, including Hodgkin's disease and other cancers of the blood.
• •21. Known tuberculosis.
• •22. Sickle cell disease.
• •23. Acquired Immune Deficiency Syndrome (AIDS) or a positive HIV antibody test.
• •24. History of illegal intravenous (IV) drug use.
• •25. Required use of concomitant medications that were excluded from the study.
• •26. Less than 12 months since a blood transfusion from another person in the United States (unless his own "autologous" blood), or exposure to someone else's blood.
• •27. Less than 6 months since diagnosis and treatment of a significant heart murmur.
• •28. Less than 12 months since treatment for syphilis or gonorrhea was completed.
• •29. Less than 60 days since participation in an investigational study in which receipt of an investigation drug or product occurred.
• •30. Evidence of visible oral cancer, as found in an oral health examination at the screening visit.