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

NCT02664012 | Completed

• 1 other identifier: CSD1501
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking

Keywords

adoption; electronic cigarettes; e-cigarettes; menthol; combustible cigarettes; nicotine polacrilex; own brand cigarette; subjective measures; pharmacokinetics; pharmacodynamics; cigarette

Outcome Measures

Primary Outcomes (17)

• 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

Other Outcomes (6)

• Maximum change in blood pressure relative to baseline

  Baseline and at timed intervals over 360 minutes following initiation of IP use

• 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

  -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes

• 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

  -10, 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 minutes

Study Arms (5)

Own Brand Menthol Cigarette

ACTIVE COMPARATOR

Own Brand Menthol Cigarette

Other: Own Brand Menthol Cigarette

Electronic Menthol Cigarette #1

EXPERIMENTAL

VUSE® (menthol flavor, 14 mg nicotine)

Other: Electronic Menthol Cigarette #1

Electronic Menthol Cigarette #2

EXPERIMENTAL

VUSE® (menthol flavor, 29 mg nicotine)

Other: Electronic Menthol Cigarette #2

Electronic Menthol Cigarette #3

EXPERIMENTAL

VUSE® (menthol flavor, 36 mg nicotine)

Other: Electronic Menthol Cigarette #3

Leading U.S. Nicotine Gum

ACTIVE COMPARATOR

4 mg nicotine polacrilex gum

Other: Leading U.S. Nicotine Gum

Interventions

Own Brand Menthol Cigarette OTHER

combustible menthol cigarette brand style smoked most frequently by subject

Own Brand Menthol Cigarette

Electronic Menthol Cigarette #1 OTHER

VUSE® Digital Vapor Cigarette (menthol flavor, 14 mg nicotine)

Electronic Menthol Cigarette #1

Electronic Menthol Cigarette #2 OTHER

VUSE® Digital Vapor Cigarette (menthol flavor, 29 mg nicotine)

Electronic Menthol Cigarette #2

Electronic Menthol Cigarette #3 OTHER

VUSE® Digital Vapor Cigarette (menthol flavor, 36 mg nicotine)

Electronic Menthol Cigarette #3

Leading U.S. Nicotine Gum OTHER

4 mg nicotine polacrilex gum

Leading U.S. Nicotine Gum

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• R.J. Reynolds Vapor Company: lead
• Celerion: collaborator
• RAI Services Company: collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• 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.

  PMID: 29725702 RESULT

MeSH Terms

Conditions

Smoking; Vaping

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Michael Gartner, MD

  Celerion

  PRINCIPAL INVESTIGATOR

• Charles Tomek, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2016
• First Posted: January 26, 2016
• Study Start: January 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 4, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)