Use Behavior, Nicotine Uptake, and Subjective Effects Comparison of Tobacco and Menthol e-Liquids by ENDS Consumers

A Randomized, Single-Blind, Two-Arm, Cross-Over Study to Compare Use of Two Tobacco and Two Menthol Flavor e-Liquids in Electronic Nicotine Delivery System Users

This study is being conducted to evaluate the impact of within-flavor category (tobacco and menthol) differences in e-liquid flavors on product use behaviors, nicotine uptake, and subjective effects by current ENDS consumers when used in a closed-system electronic nicotine delivery system (ENDS).

Study Overview

• Status: Completed
• Conditions: Electronic Cigarette Use
• Intervention / Treatment: Other: RELX ENDS Tobacco Flavor 1; Other: RELX ENDS Tobacco Flavor 2; Other: RELX ENDS Menthol Flavor 1; Other: RELX ENDS Menthol Flavor 2

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Los Angeles Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is 22 to 65 years of age, inclusive, at the time of consent.
2. Has used a closed-system ENDS product on most days during the 60 days prior to Screening (no use on up to 8 days total is allowed). Dual use with open-system products will be allowed provided that the closed-system is the predominant system used (based on self-reported volume of e-liquid used).
3. Reports a tobacco or menthol/mint flavored e-liquid as the most commonly used flavor (based on self-reported volume of e-liquid used) during the 30 days prior to screening.
4. Agrees to maintain product use described in Criteria 3 and 4 from Screening through Test Visit 1.
5. Has a urine cotinine concentration ≥ 200 ng/mL at Screening.
6. Has an ECO concentration < 10 ppm at Screening and Test Visit 1.

7. If female, must meet one of the following criteria:

   If of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 30 days prior to the first product use and during the study. An acceptable method of contraception includes one of the following:

   • Abstinence from heterosexual intercourse
   • Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
   • Intrauterine device (with or without hormones) OR agrees to use a double barrier method (e.g., condom and spermicide) during the study.

   If a female of non-childbearing potential - should be surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion) or in a menopausal state (at least 1 year without menses).

8. Is willing to comply with the requirements of the study.
9. Provides voluntary consent to participate in the study as documented on the signed ICF.

Exclusion Criteria:

1. Has a history or presence of clinically significant uncontrolled gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that would jeopardize the safety of the subject or impact the validity of the study results.

2. Has a clinically significant abnormal finding on the physical examination, medical history, vital signs, ECG, or clinical laboratory results at Screening, including, but not limited to, the following:

   1. Has a history of drug or alcohol abuse within 12 months of Screening.
   2. Has a systolic BP <90 mmHg or >160 mmHg, diastolic BP <40 mmHg or >95 mmHg, or HR <40 bpm or >99 bpm at Screening.
   3. Has previously been diagnosed with any form of cancer, except for basal cell or squamous epithelial carcinomas of the skin that have been resected.
   4. Has been treated chronically for depression, diabetes, asthma, emphysema, or chronic obstructive pulmonary disease within 12 months of Test Visit 1.
3. Has had an acute illness (e.g., upper respiratory infection, viral infection) within 14 days prior to Test Visit 1 that would jeopardize the safety of the subject or impact the validity of the study results.

4. Subjects who, in the judgment of the study physician, have recent or active COVID 19 infection, as evidenced by the following:

   1. Endorsement of symptoms that could indicate COVID-19 during screening and/or
   2. Body temperature ≥100.4°F and/or
   3. Laboratory test results suggestive of active or recent exposure to SARS CoV 2.
5. Has a BMI greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.
6. Is allergic to or intolerant of components of the product e-liquid, including but not limited to, menthol, propylene glycol, or glycerin.
7. Has a positive urine drug or alcohol test at Screening..
8. If female, has a positive pregnancy test, is breastfeeding or lactating, or intends to become pregnant from Screening through Test Visit 3.
9. Is a current combustible cigarette, cigar, or little cigar smoker at Screening (more than 5 product uses in the previous 30 days).
10. Has used other tobacco- or nicotine-containing products other than ENDS products (e.g., combustible cigarettes, cigars, or little cigars, snuff, pouches, chewing tobacco, nicotine inhalers, nicotine patches, nicotine sprays, nicotine lozenges, or nicotine gum) from 14 days prior to Test Visit 1.
11. Has used any products for the purpose of smoking/vaping cessation, including, but not limited to, nicotine replacement therapies, varenicline (Chantix), or bupropion (Zyban) from 30 days prior to Screening through Test Visit 3.
12. Draws aerosol from the usual brand ENDS into the mouth and throat but does not inhale as observed by the clinic staff during Screening.
13. Is postponing a planned vaping quit attempt in order to participate in the study.
14. Has donated plasma within 7 days prior to Test Visit 1.
15. Has provided a whole blood donation, had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Test Visit 1.
16. Has participated in a previous clinical study for a tobacco product or an investigational drug, device, or biologic, within 30 days or 5 times the half-life of the product (whichever is longer) prior to Test Visit 1.
17. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current or former employee of a tobacco or ENDS manufacturer (including the Sponsor) or is a named party or class representative in litigation with the tobacco or ENDS industry.
18. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the clinic site(s).
19. Has previously been withdrawn from or has completed this study.
20. In the opinion of an Investigator, the subject should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Product Use Sequence 1; Period 1 - RELX ENDS tobacco flavor 1 Period 2 - RELX ENDS tobacco flavor 2	Other: RELX ENDS Tobacco Flavor 1; 2-week ad libitum use of the RELX ENDS tobacco flavor 1; Other: RELX ENDS Tobacco Flavor 2; 2-week ad libitum use of the RELX ENDS tobacco flavor 2
Experimental: Product Use Sequence 2; Period 1 - RELX ENDS tobacco flavor 2 Period 2 - RELX ENDS tobacco flavor 1	Other: RELX ENDS Tobacco Flavor 1; 2-week ad libitum use of the RELX ENDS tobacco flavor 1; Other: RELX ENDS Tobacco Flavor 2; 2-week ad libitum use of the RELX ENDS tobacco flavor 2
Experimental: Product Use Sequence 3; Period 1 - RELX ENDS menthol flavor 1 Period 2 - RELX ENDS menthol flavor 2	Other: RELX ENDS Menthol Flavor 1; 2-week ad libitum use of the RELX ENDS menthol flavor 1; Other: RELX ENDS Menthol Flavor 2; 2-week ad libitum use of the RELX ENDS menthol flavor 2
Experimental: Product Use Sequence 4; Period 1 - RELX ENDS menthol flavor 2 Period 2 - RELX ENDS menthol flavor 1	Other: RELX ENDS Menthol Flavor 1; 2-week ad libitum use of the RELX ENDS menthol flavor 1; Other: RELX ENDS Menthol Flavor 2; 2-week ad libitum use of the RELX ENDS menthol flavor 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study product use - daily pod use	The number of pods used per day during the 14-day ambulatory period	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study product use - e-liquid consumption per pod	The amount of e-liquid consumed per pod during the 14-day ambulatory period	14 days
Study product use - e-liquid consumption per day	The amount of e-liquid consumed each day during the 14-day ambulatory period	14 days
Puff topography - number of puffs	Number of puffs taken from the study products during the PK Session	5 minutes
Puff topography - duration of puffs	Duration of puffs taken from the study products during the PK Session	5 minutes
Puff topography - volume of puffs	Volume of puffs taken from the study products during the PK Session	5 minutes
Puff topography - peak flow rate of puffs	Peak flow rate of puffs taken from the study products during the PK Session	5 minutes
Puff topography - average flow rate of puffs	Average flow rate of puffs taken from the study products during the PK Session	5 minutes
Puff topography - inter-puff interval	Inter-puff interval of puffs taken from the study products during the PK Session	5 minutes
Study product use - e-liquid consumption (PK session)	Change in pod weight of pods used during the PK Session	5 minutes
Subjective effects - dependence	Nicotine dependence as measured by the Penn State Electronic Cigarette Dependence Index (PSECDI) total score. Total scores may range from 0 to 20, with higher levels of dependence associated with higher scores.	14 days
Subjective effects - craving	Craving as measured by the Questionnaire of Vaping Craving (QVC) average score. Questionnaire responses are measured on a Likert scale range of 1 [strongly disagree] to 7 [strongly agree].	14 days
Subjective effects - withdrawal symptoms	Withdrawal symptoms as measured by the Minnesota Tobacco Withdrawal Scale - Revised (MTWS-R), which includes the DSM-5 and craving items from the MTWS. Questionnaire responses are measured on a Likert scale range of 0 [none] to 4 [severe]).	14 days
Subjective effects - product effects	Product effects as measured by the Modified Product Evaluation Scale (mPES) satisfaction, psychological reward, aversion, and relief subscale and individual item scores. Questionnaire responses are measured on a Likert scale range of 1 [not at all] to 7 [extremely].	14 days
Subjective effects - future intent to use product	Future intent to use the product as measured by the Future Intent to Use Questionnaire (FIU). Questionnaire responses are measured on a Likert scale range of 1 [extremely unlikely] to 7 [extremely likely].	14 days
Subjective effects - maximum acute urge to vape reduction	Maximum urge to vape reduction (Emax_R) as measured by responses to the Urge to Vape questionnaire (visual analog scale range of "Not at All" to "Extreme")	30 minutes
Subjective effects - overall acute urge to vape reduction	Overall urge to vape reduction (AOEC0-30) as measured by responses to the Urge to Vape questionnaire (visual analog scale range of "Not at All" to "Extreme")	30 minutes
Subjective effects - time to maximum acute urge to vape reduction	Time to the maximum urge to vape reduction (TEmax_R) as measured by responses to the Urge to Vape questionnaire (visual analog scale range of "Not at All" to "Extreme")	30 minutes
Nicotine uptake - maximum nicotine concentration	Baseline-adjusted maximum plasma nicotine concentration [Cmax]	30 minutes
Nicotine uptake - overall nicotine uptake	Baseline-adjusted area under the nicotine concentration-time curve [AUC(0-30)]	30 minutes
Nicotine uptake - time to maximum nicotine concentration	Time of the maximum post-baseline nicotine concentration [Tmax]	30 minutes
Safety and tolerability - adverse events	Incidence of product-use emergent adverse events	14 days
Safety and tolerability - product malfunction or misuse	Incidence of product malfunction or misuse	14 days

Collaborators and Investigators

• Sponsor: Cheerain HK Limited
• Investigators: Study Director: Donald Graff, PharmD, RELX International

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2021
• Primary Completion (Actual): November 12, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: November 13, 2021
• First Submitted That Met QC Criteria: November 13, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Nicotine; Electronic Nicotine Delivery System; E-cigarette; Topography; Subjective effects
• Additional Relevant MeSH Terms: Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: RELX-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No