Pharmacokinetic and Subjective Effects of Heated Tobacco Products

Exclusion Criteria

• •1. Use of any HTPs within the past 30 days prior to the screening visit; occasional use (i.e., not daily use) of other types of tobacco- or nicotine-containing products other than factory manufactured combustible cigarettes (e.g., roll-your-own cigarettes, e-cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) are allowed within the past 30 days prior to screening.
• •2. Any postponement of a quit attempt to participate in the study; or any attempts to quit smoking in the 3 months prior to Day -1 (Check-in).
• •3. Self-reported puffers (i.e., smokers who draw smoke from the combustible cigarette into the mouth and throat but do not inhale).
• •4. Poor dentition that prevents participant from using nicotine gum.
• •5. History or presence of any type of malignant tumor or clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would interfere with the absorption, distribution, metabolism, or excretion of cotinine or jeopardize the safety of the participant or impact the validity of the study results.
• •6. Current evidence or any history of congestive heart failure.
• •7. Any other condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study, or unable or unwilling to comply with the study procedures.
• •8. Clinically significant abnormal vital sign, physical examination (including oral cavity an oropharynx), medical history, or clinical laboratory finding(s), in the opinion of the Investigator.
• •9. Positive test for human immunodeficiency virus (HIV)-1 or HIV-2; or hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) consistent with current infection at screening.
• •10. Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator. Fasting plasma glucose \> 126 mg/dL (7 mmol/L) is exclusionary. One recheck may be performed for fasting plasma glucose values \> 126 mg/dL but \< 200 mg/dL.
• •11. An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to Check-in.
• •12. History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study through EOS.
• •13. History of alcohol abuse or drug abuse within 24 months prior to Check-in.
• •14. Consumption of alcohol-containing food or beverages within 48 hours prior to Check-in.
• •15. Positive screen for alcohol (breath or urine) or any of the following drugs of abuse (urine), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or Check-in.
• •16. Fever (i.e., body temperature \> 100.5°F) at screening or Check-in; 1 recheck may be performed at the Investigator's discretion.
• •17. Body mass index (NHLBI) \> 40.0 kg/m2 or \< 18.0 kg/m2 at screening.
• •18. Estimated glomerular filtration rate \< 80 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (Medscape) at screening.
• •19. Serum alanine aminotransferase ≥ 1.5 times the upper limit of normal and/or aspartate aminotransferase ≥ 2.0 times the upper limit of normal at screening; 1 recheck may be performed at the Investigator's discretion.
• •20. Female participants who are pregnant (positive pregnancy test at screening or Check-in), lactating, or intend to become pregnant from screening through EOS.
• •21. Use of prescription or over-the-counter (OTC) bronchodilator medication (e.g., inhaled or oral β-agonists) for treatment of any illness within 12 months prior to Check-in.
• •22. Use of antibiotics within 2 weeks prior to Check-in. Also refer to Section 5.7.1.
• •23. Use of medications known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, 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 Check-in.
• •24. Has taken other investigational drugs/products or participated in any clinical study for an investigational drug, device, biologic, or for a tobacco product within 30 days or 5 halflives (if known) of the investigational product's PK, pharmacodynamic, or biological activity (if known), whichever is longer, prior to first administration of study product in this study or is currently participating in another clinical study; or participation in \> 2 ALCS-sponsored studies within the past 12 month period prior to Check-in.
• •25. Has received a vaccination within 14 days prior to Check-in.
• •26. Plasma donation within 7 days prior to Day 1.
• •27. Donation of ≥ 1 unit of blood or blood products (with the exception of plasma as noted), had significant blood loss \> 450 mL, or received whole blood or a blood product transfusion within 56 days prior to Day -1.
• •28. Strenuous activity (as assessed by the Investigator) within 48 hours prior to Check-in.
• •29. Participant or a first-degree relative (i.e., parent, sibling, child, spouse) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company.
• •30. Participant or a first-degree relative (i.e., parent, sibling, child, spouse) is a current employee of the study site.
• •31. Unwilling or unlikely to comply with the requirements of the study.