Biomarkers of Exposure and Biomarkers of Potential Harm in Adult Smokers Who Completely Switch to E-vapor Products

Inclusion Criteria

Study 1

Subjects must satisfy the following criteria before being enrolled into the study. Subjects must:

• sign an IRB-approved informed consent form (ICF) for the study;
• be between the ages of 30 and 65 years, inclusive, at the time of Screening, Visit 1;
• have > 500 ng/ml urine cotinine measurement at Screening, Visit 1;
• have smoked for ≥ 10 years and smoked an average of ≥ 10 manufactured cigarettes per day during the 12 months prior to Screening, Visit 1;

a) Brief periods [i.e., up to 7 consecutive days] of non smoking during the 12 months prior to Screening, Visit 1 due to illness, trying to quit, or participation in a study where smoking was prohibited are acceptable.

• indicate that he/she is "definitely" or "probably" willing and able to replace their cigarettes for 12 weeks with the assigned test e-Vapor product;
• have daily access to text messaging capable cellular phone for daily product use reporting;
• have a negative ethanol breath test and amphetamines, opiates, cannabinoids, and cocaine urine drug screen results at Screening, Visit 1;

a) Subjects with a prescription from a licensed physician will not be exempted from this criterion.

• if female (all females), have a negative serum pregnancy test at Visit 1 and negative urine pregnancy test at Visit 2 through Visit 7, inclusive;
• if female, heterosexually active, and of childbearing potential (i.e., not surgically sterile or 2 years naturally postmenopausal), must have used a medically accepted method of contraception (listed below in a) and b)) prior to Screening, Visit 1 and must agree to continue to use such method(s) through the End of Study;
• Surgically sterile includes bilateral tubal ligation, Essure, hysterectomy, or bilateral oophorectomy at least 6 months prior to Screening, Visit 1. Naturally postmenopausal is defined as women having 2 years without menses.
• Acceptable methods of contraception are: hormonal (i.e., oral, transdermal patch, implant, or injection) consistently for at least 3 months prior to Screening, Visit 1; double barrier (i.e., condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to Screening, Visit 1; and intrauterine device for at least 3 months prior to Screening, Visit 1; or only have a partner who has been vasectomized for at least 6 months prior to Screening, Visit 1.
• Be willing and able to comply with the requirements of the study.

Study 2

Subjects must satisfy the following criteria before being enrolled into the study. Subject must:

• have participated in and completed the 12-week ALCS-RA-16-06-EV study and have Baseline biomarker samples collected;
• demonstrate willingness to participate by signing an Institutional Review Board (IRB)-approved ICF for the study;
• have demonstrated consistent daily reporting of product use in the 12-week ALCS-RA-16-06-EV (≥ 80% reporting compliance);
• if randomized to a Test group, have reported an average of no more than 10% of Baseline cigarette smoking per day through Week 11 of the 12-week ALCS-RA-16-06-EV study;
• if randomized to a Test group, have reported use of at least two Test product cartridges per week in the 12-week ALCS-RA-16-06-EV study;
• if randomized to a Test group, have exhaled carbon monoxide (eCO) measurements of ≤ 8 ppm at each post-Baseline time point in the 12-week ALCS-RA-16-06-EV study;
• have daily access to text messaging capable cellular phone for daily product use reporting;
• if female (all females), have a negative urine pregnancy test at Week 12 (Visit 1) through Week 24 (Visit 5), inclusive;
• if female, heterosexually active, and of childbearing potential (i.e., not surgically sterile or 2 years naturally postmenopausal), must have used a medically accepted method of contraception (listed below in a) and b)) prior to Screening, Visit 1 of the 12-week ALCS-RA-16-06-EV study and must agree to continue to use such method(s) through Week 24 (EOS);
• Surg