A Study to Assess Nicotine Uptake From Electronic Nicotine Delivery System Products

This will be a randomized, open-label, 8-way crossover, single-site study designed to evaluate elements of abuse liability (AL), including subjective effects and physiological measures (pharmacodynamics \[PD\]), and plasma nicotine uptake (pharmacokinetics \[PK\]) during and following ad libitum use of electronic nicotine delivery system (ENDS) investigational products (IPs). The study will be conducted in a confinement setting among generally healthy adult smokers of combustible cigarettes and dual users of cigarettes and ENDS products.

Inclusion Criteria: 1. Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English. 2. Generally healthy male or female, 21 to 60 years of age, inclusive, at the time of consent. 3. Expired breath carbon monoxide level is ≥ 10 ppm and ≤ 100 ppm at Screening. 4. Positive urine cotinine test at Screening. 5. Smokes combustible filtered, menthol or non-menthol cigarettes, 83 mm to 100 mm in length. 6. Agrees to smoke same UB cigarette throughout the study period. UB cigarette is defined as the cigarette brand style currently smoked most frequently by the participant. 7. Participants must meet one (a or b) of the following tobacco use conditions: a. Sole smoker of filtered menthol or non-menthol cigarettes who self reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (more than 30 days prior to Screening), or clinical study participation (more than 30 days prior to Screening) will be allowed at the discretion of an investigator b. Dual user of cigarettes and ENDS who self-reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening Visit. Brief periods of abstinence more than 30 days prior to screening due to illness, quit attempt or clinical study participation will be allowed at the discretion of an investigator, and ii. Using a nicotine-containing ENDS (cartridge or a tank system). NOTE: Cigarette smokers or ENDS users who also use other tobacco- or nicotine-containing products (e.g., smokeless tobacco, and modern oral nicotine products) on no more than one day per week will not be excluded from study participation. 8. Response at Screening to the Fagerström Test for Nicotine Dependence (FTND) Question 1 ("How soon after you wake up do you smoke your first cigarette?") is either "Within 5 minutes" or "6-30 minutes." 9. Willing to use only UB cigarettes and ENDS IPs during the study period. 10. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each test session. 11. Females must be willing to use a form of contraception acceptable to an investigator from the time of signing informed consent until End-of-Study. Examples of acceptable means of birth control include, but are not limited to: 1. Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy); 2. Physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide; 3. Non-hormone releasing intrauterine devices (IUDs) or hormone-releasing IUDs (e.g., Mirena or Kyleena); 4. Vasectomized partner; 5. Post-menopausal and not on hormone replacement therapy; or 6. Sexual abstinence, defined as refraining from intercourse, when this is in line with the preferred and usual lifestyle of the participant. 12. Males must use an acceptable method of birth control from Day -1 "check-in" until the end of the study, unless they have had a vasectomy or are abstinent from heterosexual intercourse, or their female partner is not able to bear children. 13. Agrees to in-clinic confinement of 10 days and 9 nights. Exclusion Criteria: 1. Presence of clinically significant uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, psychiatric, hematological, neurological disease, or any other concurrent disease or medical condition that, in the opinion of an investigator, makes the study participant unsuitable to participate in this clinical study. 2. History, presence of, or clinical laboratory test results indicating diabetes. 3. Systolic blood pressure of \> 160 mmHg or a diastolic blood pressure of \> 95 mmHg, measured after being seated for five minutes at Screening and at check-in Day -1. 4. Weight of ≤ 110 pounds (≤ 50.0 kg) at Screening. 5. Hemoglobin level is \< 12.5 g/dL for females or \