Comparison of Nicotine Plasma Concentrations and Subjective Effects for Three Menthol Electronic Cigarettes vs Combustible Menthol Cigarettes and Nicotine Gum

Study Overview
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Brief Summary
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The purpose of this study is to measure plasma nicotine uptake parameters, physiological measures, and subjective effect measures in smokers during and following a single ad libitum use of three menthol electronic cigarettes versus combustible menthol cigarettes and nicotine gum.

Detailed Description
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This study will assess various elements that may provide information regarding the potential for menthol electronic cigarettes (e-cigarettes) to be adopted by current smokers. These various elements include: a) nicotine pharmacokinetics (PK), b) physiological measures of pulse rate and blood pressure, and c) subjective effects measured by Urge to Smoke, Urge for Product, Product Rating, Intent to Use Product Again, and Product Effects.

Official Title
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A Single-Center, Randomized, Open-Label, Crossover Study to Assess Elements of Abuse Liability for Three Menthol Electronic Cigarettes

Conditions
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Smoking

Intervention / Treatment
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* Other: Own Brand Menthol Cigarette
* Other: Electronic Menthol Cigarette #1
* Other: Electronic Menthol Cigarette #2
* Other: Electronic Menthol Cigarette #3
* Other: Leading U.S. Nicotine Gum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read, understand, and willing to sign an informed consent form and complete questionnaires written in English. Generally healthy male or female, 21 to 60 years of age, inclusive, at Screening. Expired breath carbon monoxide (ECO) level is ≥ 15 ppm and ≤ 100 ppm at the Screening and Randomization Visits, measured between 12 p.m. and 6 p.m. Combustible menthol cigarettes are the only tobacco product used within (≤) 30 days of Screening. Smokes combustible, filtered, menthol cigarettes, 83 mm to 100 mm in length. Agrees to smoke usual brand (UB) menthol cigarette throughout the study period. Usual brand cigarette is defined as the menthol cigarette brand style currently smoked most frequently by the subject. Smokes at least 10 menthol 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 (prior to 30 days of Screening), or clinical study participation (prior to 30 days of Screening) will be allowed at the discretion of the Investigator. Response at Screening to Fagerstrom Test for Nicotine Dependence, 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 UB menthol cigarette, the study electronic cigarette menthol brand styles and nicotine gum during the study period. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to check-in at each Test Visit. Females of childbearing potential must be willing to use a form of contraception acceptable to the Investigator from the time of signing informed consent until study discharge. Exclusion Criteria: 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., uncontrolled hypertension, asthma or other lung disease, cardiac disease, neurological disease or psychiatric disorders) based on safety assessments such as clinical laboratory tests, medical history, and physical/oral examinations. Systolic blood pressure of > 150 mmHg or a diastolic blood pressure of > 95 mmHg at Screening, measured after being seated for at least 5 minutes. Hemoglobin level is < 12 g/dL at Screening. Positive test for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, or Hepatitis C virus. Postponing a decision to quit smoking (defined as planning a quit attempt within [≤] 30 days of Screening) to participate in this study or previous attempt within (≤) 30 days prior to Screening. Employed by a tobacco company, the study site, or handles unprocessed tobacco as part of their job. Use of any medication or supplement that aids smoking cessation, including but not limited to any nicotine replacement therapy (e.g., nicotine gum, lozenge, patch), varenicline (Chantix), bupropion (Wellbutrin, Zyban), or lobelia extract within (≤) 30 days of Screening. Females ≥ 35 years of age currently using systemic, estrogen containing contraception or hormone replacement therapy. A positive urine drug screen without disclosure of corresponding prescribed concomitant medication(s), at Screening or Randomization Visit. A positive alcohol result at Screening, Randomization Visit, or at any Test Visit. A female who is pregnant, lactating, or intends to become pregnant during the course of the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Own Brand Menthol Cigarette<br>Own Brand Menthol Cigarette | Other: Own Brand Menthol Cigarette<br>* combustible menthol cigarette brand style smoked most frequently by subject<br>|
| Experimental: Electronic Menthol Cigarette #1<br>VUSE® (menthol flavor, 14 mg nicotine) | Other: Electronic Menthol Cigarette #1<br>* VUSE® Digital Vapor Cigarette (menthol flavor, 14 mg nicotine)<br>|
| Experimental: Electronic Menthol Cigarette #2<br>VUSE® (menthol flavor, 29 mg nicotine) | Other: Electronic Menthol Cigarette #2<br>* VUSE® Digital Vapor Cigarette (menthol flavor, 29 mg nicotine)<br>|
| Experimental: Electronic Menthol Cigarette #3<br>VUSE® (menthol flavor, 36 mg nicotine) | Other: Electronic Menthol Cigarette #3<br>* VUSE® Digital Vapor Cigarette (menthol flavor, 36 mg nicotine)<br>|
| Active Comparator: Leading U.S. Nicotine Gum<br>4 mg nicotine polacrilex gum | Other: Leading U.S. Nicotine Gum<br>* 4 mg nicotine polacrilex gum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence | Determine area under the plasma nicotine concentration versus time curve (AUC) | -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence | Determine maximum plasma nicotine concentration (Cmax), baseline adjusted | -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence | Determine time to maximum plasma nicotine concentration (Tmax), baseline-adjusted | -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Urge to Smoke (UTS) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a numeric rating scale (NRS) to determine area under the UTS score-versus-time curve [area under the effect curve (AUEC)] | -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Intent to Use Again (IUA) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine area under the IUA score-versus-time curve (AUEC) | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Product Ratings (PR) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine area under the PR score-versus-time curve (AUEC) | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Positive Product Effects (PE) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine area under the Positive PE score-versus-time curve (AUEC) | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Negative Product Effects (PE) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine area under the Negative PE score-versus-time curve (AUEC) | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Maximum change in pulse rate relative to baseline | Determine the maximum change in pulse rate | Baseline and at timed intervals over 360 minutes following initiation of IP use | 
| Baseline cotinine measured pre-IP use | Evaluate changes in baseline cotinine to assess whether subjects substantially changed their nicotine uptake during the study | -0.5 minute (baseline) and -5 min (back-up baseline) for each IP | 
| Change in expired carbon monoxide (ECO) relative to baseline | Assess change in ECO from baseline following IP use | Baseline and 35 minutes post-IP use | 
| Subjective effects scores for UTS with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine minimum UTS score | -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Subjective effects scores for UTS with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine time to minimum UTS score | -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes | 
| Subjective effects scores for IUA with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine maximum IUA score | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for PR with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine maximum PR score | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Positive PE with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine maximum Positive PE score | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 
| Subjective effects scores for Negative PE with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence | Score subjective effects using a NRS to determine maximum Negative PE score | 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adoption, electronic cigarettes, e-cigarettes, menthol, combustible cigarettes, nicotine polacrilex, own brand cigarette, subjective measures, pharmacokinetics, pharmacodynamics, cigarette