Clinical trial NCT02664012: Comparison of Nicotine Plasma Concentrations and Subjective Effects for Three Menthol Electronic Cigarettes vs Combustible Menthol Cigarettes and Nicotine Gum
Official title: A Single-Center, Randomized, Open-Label, Crossover Study to Assess Elements of Abuse Liability for Three Menthol Electronic Cigarettes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Keywords: adoption
electronic cigarettes
e-cigarettes
menthol
combustible cigarettes
nicotine polacrilex
own brand cigarette
subjective measures
pharmacokinetics
pharmacodynamics
cigarette
Lead sponsor: R.J. Reynolds Vapor Company
Sponsor class: INDUSTRY
Collaborators: name: Celerion
name: RAI Services Company
First posted: 2016-01-26
Enrollment: 71
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Able to read, understand, and willing to sign an informed consent form and complete questionnaires written in English.
2. Generally healthy male or female, 21 to 60 years of age, inclusive, at Screening.
3. 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.
4. Combustible menthol cigarettes are the only tobacco product used within (≤) 30 days of Screening.
5. Smokes combustible, filtered, menthol cigarettes, 83 mm to 100 mm in length.
6. 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.
7. 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.
8. 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."
9. Willing to use UB menthol cigarette, the study electronic cigarette menthol brand styles and nicotine gum during the study period.
10. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to check-in at each Test Visit.
11. 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:

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., 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.
2. 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.
3. Hemoglobin level is \< 12 g/dL at Screening.
4. Positive test for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, or Hepatitis C virus.
5. 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.
6. Employed by a tobacco company, the study site, or handles unprocessed tobacco as part of their job.
7. 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.
8. Females ≥ 35 years of age currently using systemic, estrogen containing contraception or hormone replacement therapy.
9. 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.
10. A female who is pregnant, lactating, or intends to become pregnant during the course of the study.

Primary outcomes:
measure: Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence
timeFrame: -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence
timeFrame: -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Nicotine pharmacokinetics with respect to initiation of in-clinic investigational product (IP) use following a 12-hour tobacco and nicotine abstinence
timeFrame: -5, -0.5, 5, 7.5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360 minutes
measure: 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
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: 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
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: Subjective effects scores for Product Ratings (PR) with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: 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
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: 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
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: Maximum change in pulse rate relative to baseline
timeFrame: Baseline and at timed intervals over 360 minutes following initiation of IP use
measure: Baseline cotinine measured pre-IP use
timeFrame: -0.5 minute (baseline) and -5 min (back-up baseline) for each IP
measure: Change in expired carbon monoxide (ECO) relative to baseline
timeFrame: Baseline and 35 minutes post-IP use
measure: Subjective effects scores for UTS with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Subjective effects scores for UTS with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Subjective effects scores for IUA with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: Subjective effects scores for PR with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: Subjective effects scores for Positive PE with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
measure: Subjective effects scores for Negative PE with respect to initiation of in-clinic IP use following a 12-hour tobacco and nicotine abstinence
timeFrame: 15, 30, 45, 60, 120, 180, 240, 300, 360 minutes
Secondary outcomes:
Other outcomes:
measure: Maximum change in blood pressure relative to baseline
timeFrame: Baseline and at timed intervals over 360 minutes following initiation of IP use
measure: Subjective effects scores for Urge for Product (UFP) with respect to initiation of in-clinic IP use (e-cigarettes and nicotine gum only) following a 12-hour tobacco and nicotine abstinence
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Subjective effects scores for UFP with respect to initiation of in-clinic IP use (e-cigarettes and nicotine gum only) following a 12-hour tobacco and nicotine abstinence
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Subjective effects scores for UFP with respect to initiation of in-clinic IP use (e-cigarettes and nicotine gum only) following a 12-hour tobacco and nicotine abstinence
timeFrame: -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes
measure: Perform CYP2A6 genotyping
timeFrame: Once, at time of randomization
measure: Perform phenotyping (i.e., nicotine metabolic ratio of cotinine:3-hydroxy cotinine)
timeFrame: Once, at time of randomization
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Celerion
name: Michael Gartner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Celerion
name: Charles Tomek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stiles MF, Campbell LR, Jin T, Graff DW, Fant RV, Henningfield JE. Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum. Psychopharmacology (Berl). 2018 Jul;235(7):2077-2086. doi: 10.1007/s00213-018-4904-x. Epub 2018 May 3.