Changes in Biomarker of Exposure in Adults Who Smoke Cigarettes Switching From Cigarettes to Heated Tobacco Products

Exclusion Criteria

• •1. Use of any type of tobacco- or nicotine-containing products other than manufactured cigarettes (eg, e-vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to first check-in.
• •2. Self-reported puffers (ie, adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).
• •3. Planning to quit smoking in the next three months (at screening).
• •4. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, or cardiovascular disease, or any other condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• •5. Clinically significant abnormal findings on the vital signs, physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Principal Investigator.
• •6. Positive test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at screening.
• •7. History or presence of any type of malignant tumors.
• •8. Current evidence or any history of congestive heart failure.
• •9. Diabetes mellitus (fasting glucose ≥126 mg/L \[7 mmol/L\]) that is not controlled by diet/exercise alone, in the opinion of the Principal Investigator.
• •10. An acute illness (eg, upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to first check-in.
• •11. Any planned surgery from the time of screening through EOS.
• •12. History of drug or alcohol abuse within 24 months prior to first check-in.
• •13. Fever (ie, body temperature \>100.5°F) at screening or first check-in. One re-check may be performed at the Principal Investigator's discretion.
• •14. Body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at screening.
• •15. Systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 90 mmHg at screening or first check-in, measured after being seated for at least 10 minutes. Two re-checks may be performed at the Principal Investigator's discretion.
• •16. Estimated creatinine clearance (by Cockcroft-Gault equation) \< 80 mL/minute at screening.
• •17. Serum alanine aminotransferase ≥1.5 times the upper limit of normal and/or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening.
• •18. Positive screen for alcohol (urine/breath) or any of the following drugs of abuse (urine/saliva), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or first check-in.
• •19. Female subjects who are pregnant (positive serum pregnancy test at screening or urine/serum pregnancy test at first check-in), lactating, or intend to become pregnant from screening through EOS.
• •20. Use of prescription or over-the-counter bronchodilator medication (eg, inhaled or oral ß-agonists) for treatment of any illnesses and within 12 months prior to first check-in and throughout the study.
• •21. Use of medications or foods known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, grapefruit, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to first check-in or during the study.
• •22. Use of antibiotic treatment within 2 weeks prior to first check-in.
• •23. Plasma donation within 7 days prior to first check-in.
• •24. Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to first check-in.
• •25. Participation in a previous clinical study for an investigational drug, device, biologic, or a tobacco product within 30 days prior to first check-in.
• •26. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company.
• •27. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current employee of the study site.
• •28. Have been diagnosed with major depressive disorder or have a history of suicide attempt.
• •29. Have pre-bronchodilator to post-bronchodilator FEV1 increases of greater than or equal to 12% or grade "C" or worse per ATS/ERS 2019 standards.