Inclusion Criteria:
* Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
* Generally healthy male or female, 21 to 60 years of age, inclusive, at the time of consent.
* Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening.
* Positive urine cotinine test at Screening.
* Smokes combustible, filtered, menthol or non-menthol cigarettes, 83 mm to 100 mm in length.
* 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.
* Participants must meet one (a or b) of the following tobacco use conditions:
1. Smokes 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 the Principal Investigator (PI).
2. 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. 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 the PI and ii. Using a nicotine-containing ENDS (cartridge or 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 1 day per week will not be excluded from study participation.
* 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."
* Willing to use only UB cigarette and assigned test ENDS IPs during the study period.
* Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each test session.
* Females must be willing to use a form of contraception acceptable to an Investigator, including abstinence from heterosexual intercourse, from the time of signing informed consent until EOS. 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.
* Males must use an acceptable method of birth control from Day 1 Check-in until EOS, unless they have had a vasectomy or are abstinent from heterosexual intercourse, or their female partner is not able to bear children.
* Agrees to in-clinic confinement of 10 days and 9 nights.
Exclusion Criteria:
* 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 the PI, makes the study participant unsuitable to participate in this clinical study.
* History, presence of, or clinical laboratory test results indicating diabetes.
* Systolic blood pressure of \> 160 mmHg or a diastolic blood pressure of \> 95 mmHg, measured after being seated for 5 minutes at Screening and at Check-in Day 1.
* Weight of ≤ 110 pounds (≤ 50.0 kg) and body mass index of \> 40.0 kg/m2 at Screening.
* Hemoglobin level is \< 12.5 for females or \< 13.0 for males g/dL at Screening.
* Scheduled treatment for asthma currently or within the past consecutive 12 months prior to the Screening Visit. As-needed treatment, such as inhalers, may be included at the PI's discretion.
* Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
* Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed.
* Must not be a current regular user (i.e., \> 5 times per month) of any tobacco- or nicotinecontaining products other than cigarettes or ENDS within the last 6 months prior to Screening.
* Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), glucagon-like peptide-1 (GLP-1) agonists (e.g., Wegovy®, Mounjaro®, Ozempic®), or lobelia extract within ≤ 30 days prior to the signing of informed consent.
* History or presence of bleeding or clotting disorders.
* Use of daily aspirin (≥ 325 mg) or other daily anticoagulants.
* Whole blood donation within 8 weeks (≤ 56 days) prior to the signing of informed consent and between Screening and Check-in Day 1.
NOTE: Participants will be advised against scheduling a whole blood donation for at least 7 days following study completion.
• Plasma donation within ≤ 7 days prior to the signing of informed consent and between Screening and Check-in Day 1.
NOTE: Participants will be advised against scheduling a plasma donation for at least 7 days following study completion.
* Participation in another clinical trial within ≤ 30 days prior to the signing of informed consent. The 30-day window for each participant will be derived from the date of the last study event in the previous study to the time of signing the ICF in the current study.
* Females who have a positive pregnancy test at Screening or Check-in on Day 1, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
* Individuals ≥ 35 years of age currently using systemic, estrogen-containing contraception or hormone replacement therapy.
* Has positive urine drug screen or alcohol test (urine or breath) at Screening or at Checkin to the Assessment Phase (Day 1), with the exception of positive results for tetrahydrocannabinol (THC). If positive for THC at Check-in (Day 1), a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of an Investigator.
* Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or a previous quit attempt within ≤ 30 days prior to the signing of the ICF.
* Has a significant history of alcoholism or drug abuse within 24 months prior to Screening, as determined by the PI, or has a positive alcohol test at Screening or Checkin on Day 1.
* Employed by a tobacco or nicotine company, the study site, or handles tobacco- or nicotine-containing products as part of their job.
* Individuals or their family members who have ongoing litigation with tobacco company(ies).
* Determined by the PI to be inappropriate for this study.
