A Study to Evaluate Changes in Smokers Using An Oral Tobacco-Derived Nicotine Product

Study Overview
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Brief Summary
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The purpose of this study was to estimate changes in biomarkers of exposure (BOE) in adult cigarette smokers using an oral tobacco-derived nicotine (OTDN) product relative to adult smokers who continue smoking exclusively.

Detailed Description
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This was a randomized, controlled, open-label, parallel group, multicenter, 9-week study to determine changes in BOE in adult smokers allowed ad libitum use of an OTDN product relative to adult smokers who were not allowed to use an OTDN product. This study was conducted in adult smokers who were considered to be in overall good health. Subjects were randomized to Test (allowed OTDN use) or Control (not allowed OTDN use) groups.

Official Title
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A Randomized, Controlled, Parallel Group Clinical Study of Cigarette Smokers Using an Innovative Oral Tobacco-derived Nicotine Product to Determine Impact on Cigarette Consumption and Biomarkers of Exposure

Conditions
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Tobacco Use

Intervention / Treatment
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* Other: Oral tobacco-derived nicotine product (OTDN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must: sign an Institutional Review Board (IRB)-approved ICF for the study. be between the ages of 21 and 65 years, inclusive, at the time of Screening. have consumed a minimum of 10 manufactured CPD daily during the last 6 months (entire 6 month period must have occurred after subject turned 21 years of age). indicate that he/she smokes cigarettes every day at Screening and on Day 1 be able to fully comprehend the English language. have an active phone number and must have daily access to a touchtone phone between 1600 and 1900 hours. be interested in alternative tobacco products to cigarettes at Screening. indicate that they definitely would buy or probably would buy on the VBM-FG2 Potential Purchase Interest Questionnaire. be in generally good health. if female, have a negative urine dipstick pregnancy test. if female heterosexually active and of childbearing potential (i.e., not surgically sterile or two years naturally postmenopausal), agree to use a medically accepted method of contraception from Screening through the End of Study. have clinical laboratory tests within the appropriate reference range or which are clinically acceptable to the Investigator. have a negative ethanol, amphetamines, opiates, cannabinoids, and cocaine urine drug screen. test negative for human immunodeficiency (HIV), hepatitis B (hepatitis B surface antigen [HBsAg]), and Hepatitis C (anti-hepatitis C virus antibody [anti-HCV]). be willing and able to comply with the requirements of the study. Exclusion Criteria: Subject must not: be pregnant, nursing, or planning to become pregnant during the study period. indicate that he/she intends to quit smoking within the next 30 days (at Screening or on Day 1). have uncontrolled hypertension, history of coronary heart disease or other significant heart conditions, and/or other significant medical conditions that might interfere with study procedures. have used prescription anti-diabetic medication and/or insulin therapy within 12 months of Day 1. have a history of drug or alcohol abuse within the 24 months prior to Screening. have participated in a clinical study for an investigational drug, device, or biologic within 30 days prior to enrollment (Day 1). be a current user of nicotine replacement therapy (indicate every day or some days on Subject Screener/Tobacco History Questionnaire). be a current or former employee of the tobacco industry or a first-degree relative (e.g., parent, sibling, child) of a current or former employee of the tobacco industry. have been involved in the development of the study design/conduct or be a first-degree relative (e.g., parent, sibling, child) of someone involved in the development of the study design/conduct. be a current employee or personnel involved with the study at the study site. be currently participating in the study at a different study site (i.e., each subject can only be in the study population once).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group 1: Continue Smoking<br>Subjects were asked to continue smoking their own brand of cigarettes ad libitum for 4 weeks | |
| Experimental: Group 2: OTDN<br>Subjects were allowed to continue smoking their own brand of cigarettes ad libitum and provided the option to use an OTDN (specifically, VERVE® Discs Blue Mint) also under ad libitum conditions | Other: Oral tobacco-derived nicotine product (OTDN)<br> <br> * Other names: VERVE® Discs Blue Mint;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Total NNAL | Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL] (ng/g creatinine) | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Equivalents | Nicotine equivalents including nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide) (mg), urinary | 5 weeks | 
| S-PMA | S-phenyl mercapturic acid (ng/g creatinine), urinary | 5 weeks | 
| CO | Carbon monoxide (ppm), exhaled | 5 weeks | 
| COHb | Carboxyhemoglobin (%), blood | 5 weeks | 
| Product use behavior | Number of each product used per day (cigarettes and OTDN) | 5 weeks | 
| Fagerström Test for Cigarette Dependence (FTCD) | Questionnaire scored 0-10 points with Total Score equal to the sum of all points | 5 weeks | 
| Quit attempts | Number of self-reported attempts to quit smoking in the previous 30 days (How many times during the past 30 days have you stopped smoking cigarettes for 24 hours or longer because you were trying to quit?). | 5 weeks | 
| Quitting intentions | Yes/No response to Are you planning to quit smoking in the next 30 days? | 5 weeks |