CSD170302: Study to Assess Nicotine Uptake in Smokers From Electronic Cigarettes

This will be a single-center, randomized, open-label, parallel study during which up to 140
healthy adult subjects, consisting of 35 subjects per marketed EC product, will be enrolled.
Subjects will be evaluated for plasma nicotine uptake, as well as overall product liking. The
study will involve the use of four (4) marketed EC products in tobacco consumers who are
exclusive smokers (i.e., naïve EC users) or dual users of cigarettes and ECs (i.e.,
intermittent EC users).

Inclusion Criteria:

1. Able to read, understand, and willing to sign an ICF and complete questionnaires
written in English.

2. Generally healthy males and females, 21 to 60 years of age, inclusive, at Screening
Visit.

3. Subjects must meet one (a or b) of the following tobacco use conditions:

1. Exclusive cigarette smoker who self-reports smoking at least (≥) 10 cigarettes
per day 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 the
Investigator.

2. Dual user of combustible cigarettes and electronic cigarettes (EC) who
self-reports:

i. Smoking at least (≥) 10 cigarettes per day 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 the Investigator and ii. Using a nicotine-containing cig-a-like EC or a
tank system EC either daily or at least weekly for at least 3 months prior to
Screening Visit.

4. Willing to be confined overnight and abstain from tobacco- and nicotine- containing
product use for 12 hours prior to IP use through Study Discharge.

5. Willing to use assigned IP during the study according to protocol.

6. Expired breath carbon monoxide (ECO) level is ≥10 parts per million (ppm) at the
Screening Visit and Study Day 1.

7. Positive urine cotinine test at the Screening Visit and Study Day 1.

8. No intent to quit smoking or vaping from the Screening Visit to Study Day 2.

9. Females must be willing to use a form of contraception acceptable to the Investigator
from the time of signing informed consent until Study Discharge, or be surgically
sterile for at least 90 days prior to the Screening Visit.

Exclusion Criteria:

1. Presence of clinically significant or unstable/uncontrolled acute or chronic medical
conditions at the Screening Visit, as determined by the Investigator, that would
preclude a subject from participating safely in the study (e.g., uncontrolled
hypertension, diabetes, asthma or other lung disease, cardiac disease, neurological
disease or psychiatric disorders) based on safety assessments such as clinical
laboratory tests, pregnancy tests, medical history, and physical/oral examinations.

2. At risk for heart disease, as determined by the Investigator.

3. Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg,
measured after being seated for 5 minutes.

4. Weight of ≤ 110 pounds.

5. Poor peripheral venous access.

6. Use of medicine for treatment of depression, unless on a stable dose for the past 6
months prior to screening and deemed clinically stable by the PI.

7. Current scheduled treatment for asthma within the past consecutive 12 months prior to
screening. As needed treatment, such as inhalers, may be included at the PIs
discretion pending approval from the medical monitor.

8. 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.

9. Use of any medication or substance that aids in smoking cessation, including but not
limited to any nicotine replacement therapy (NRT) (e.g., nicotine gum, lozenge,
patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), or lobelia extract
within 30 days prior to the Screening Visit.

10. History or presence of hemophilia or other bleeding disorders.

11. History or presence of clotting disorders with concomitant use of anticoagulants
(e.g., clopidogrel [Plavix®], warfarin [Coumadin®, Jantoven®] or aspirin [> 325
mg/day]).

12. Participation in another clinical trial within (≤) 30 days prior to the time of
consent. The 30-day window for each subject will be derived from the date of the last
study event in the previous study to the time of consent of the current study.

13. Positive test for human immunodeficiency virus (HIV), Hepatitis B surface antigen
(HBsAg), or Hepatitis C virus antibody (anti-HCV).

14. Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to
become pregnant during the course of the study.

15. Females ≥ 35 years of age currently using systemic, estrogen-containing contraception
or hormone replacement therapy.

16. A positive urine drug screen without disclosure of prescribed corresponding
concomitant medication(s) at the Screening Visit or on Study Day 1.

17. A positive alcohol breathalyzer result at the Screening Visit or on Study Day 1.

18. Employed by a tobacco or nicotine company, the study site, or handles tobacco or
nicotine-containing products as part of their job.

19. Determined by the Investigator to be inappropriate for the study, including a subject
who is unable to communicate or unwilling to cooperate with the clinical staff.