CSD170501: Study to Assess Biomarkers of Tobacco Exposure in Smokers During In-Clinic Confinement Switch to an Electronic Cigarette

This will be a two-center, randomized, controlled, switching, open-label, parallel cohort
study. The study will compare biomarkers of tobacco exposure from subjects at baseline levels
of biomarkers of tobacco exposure after they have switched to one of three electronic
cigarettes or abstinence for 5 days.

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 males or females, 21 to 60 years of age (inclusive);

3. Screening expired carbon monoxide (ECO) level ≥ 12 parts per million (ppm);

4. Self-reports that cigarettes are the only tobacco or nicotine-containing product used
within 30 days of the Screening Visit (Note: Rare use of other products [e.g., cigar
or bridging therapy with NRT] may be acceptable in consultation with the Sponsor);

5. Self-reports at the Screening Visit smoking on average at least 10 cigarettes per day
that are filtered, non-menthol, 83 mm to 100 mm length and inhaling the smoke for at
least 6 months prior to the Screening Visit (Note: Smokers who use menthol cigarette
products like Camel Crush are not eligible for the study);

6. Positive urine cotinine test at Screening and Enrollment;

7. Willing to switch from current cigarette to one of the Investigational Products or to
abstain from smoking for approximately 7 days during in-clinic confinement;

8. Females of childbearing potential must be willing to use a form of contraception
acceptable to the Investigator from the time of signing the ICF until Study Discharge
or be surgically sterile for at least 90 days prior to the Screening Visit;

9. Able to safely perform the required study procedures, as determined by the
Investigator.

Exclusion Criteria:

1. Clinically significant or unstable/uncontrolled acute or chronic medical conditions at
screening, as determined by the Investigator, that would preclude a subject from
participating safely in the study (e.g., hypertension, chronic lung disease, heart
disease, neurological disease, or psychiatric disorders) based on screening
assessments such as safety labs, medical history, and physical/oral examinations;

2. Self-reports or safety labs that indicate diabetes;

3. 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.

4. 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.

5. 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.

6. Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg,
measured after being seated for 5 minutes (at Screening or Day -2 Check-in);

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

8. Clinically significant hemoglobin level, < 5% of the Lower Limit of Normal (LLN), as
determined by the Investigator at Screening;

9. History or presence of hemophilia or any other bleeding or clotting disorders;

10. Use of anticoagulants (e.g., clopidogrel [Plavix®], warfarin [Coumadin®, Jantoven®],
aspirin [> 325 mg/day]) at least 30 days prior to screening;

11. Given a whole blood donation within 8 weeks (≤56 days) prior to enrollment;

12. Plasma donation within ≤ 7 days prior to enrollment;

13. Weight of ≤ 110 pounds;

14. Postponing a decision to quit smoking (defined as planning a quit attempt within 30
days of Screening) to participate in this study;

15. Employed by a tobacco company, the clinical study site, or handles e-liquids or
unprocessed tobacco as part of his/her job;

16. Use of any medication or supplement that aids in smoking cessation including, but not
limited to, any nicotine replacement therapy (NRT) unless used for short term bridging
therapy (e.g., nicotine gum, lozenge, patch), varenicline (Chantix), bupropion
(Wellbutrin, Zyban), or lobelia extract within 30 days of the Screening Visit;

17. Use of injectable forms of medication(s) for the duration of the study, unless
acceptable in the opinion of the Investigator or with the exception of injectable
forms of birth control that are not required to be administered during the study
period;

18. Self-reports drinking more than 14 servings of alcoholic beverages per week (1 serving
= 12 oz of beer, 6 oz of wine, or 1.5 oz of liquor);

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

20. Females ≥35 years of age currently using systemic, estrogen-containing contraception,
or hormone replacement therapy for menopause-related symptoms;

21. A positive urine drug screen without disclosure of corresponding prescribed
concomitant medication(s) at the Screening Visit or Enrollment;

22. A positive alcohol test at Screening or Enrollment;

23. Regularly exposed to solvent fumes or gasoline (e.g., painter, auto mechanic);

24. Participation in another clinical study 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 time of consent of the current study;

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

26. Unable or unwilling to participate in the in-clinic confinement for the full study
duration (total of 10 days).