Nicotine Uptake, Measures of Abuse Liability, and Puffing Topography With Use of RELX ENDS Products by ENDS Consumers

A Randomized, Open-Label, Multi-Center, Cross-Over Study of Adult Electronic Nicotine Delivery Systems (ENDS) Consumers to Assess Nicotine Uptake, Measures of Abuse Liability, and Puffing Topography With RELX Infinity ENDS

This study is being conducted to evaluate nicotine uptake, the potential abuse liability, and puffing topography associated with the use of an electronic nicotine delivery system (ENDS) with tobacco- and menthol-flavored e-liquids in current ENDS consumers.

Study Overview

• Status: Completed
• Conditions: Electronic Cigarette Use
• Intervention / Treatment: Other: RELX ENDS Tobacco Flavor; Other: RELX ENDS Menthol Flavor; Other: Subject Usual Brand ENDS

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, Inc
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences Clinical Kansas, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provides voluntary consent to participate in the study as documented on the signed informed consent form (ICF).
2. Is 22 to 59 years of age, inclusive, at the time of consent.
3. Has been a daily ENDS consumer for at least 3 months prior to Screening and through Check-in. Brief periods of abstinence (e.g., up to ~7 consecutive days due to illness, trying to quit, participation in a study where vaping was prohibited) ≥ 30 days prior to Screening will be permitted at the discretion of an Investigator.
4. Reports weekly use of at least 3 mL of e-liquid from an ENDS product at Screening.
5. Has a urine cotinine concentration ≥ of 200 ng/mL at Screening and Check-in.
6. Has an exhaled carbon monoxide (ECO) concentration < 10 ppm at Check-in.

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, during the study, and for at least 30 days after the last product use. 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 and for at least 30 days after the last product use.

   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), as confirmed by FSH levels (≥ 40 mIU/mL).

8. Is willing to comply with the requirements of the study.

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.
3. Has a positive test for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen, or Hepatitis C Antibody.
4. Has had an acute illness (e.g., upper respiratory infection, viral infection) within 14 days prior to Check-in.
5. Has a fever (> 100.5°F) at Screening or Check-in.
6. Has a positive COVID-19 test during the screening period, prior to Check-in.
7. Has a body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening.
8. Has a history of drug or alcohol abuse within 12 months of Screening.
9. Has a systolic BP < 90 mmHg or > 150 mmHg, diastolic BP < 40 mmHg or > 95 mmHg, or HR < 40 bpm or > 99 bpm at Screening.
10. Is allergic to or intolerant of components of the product e-liquid, including but not limited to, menthol, propylene glycol or glycerin.
11. Is unable to use the CReSS topography device with the vaping device during the training session on Day -1.
12. Has an estimated creatinine clearance < 70 mL/minute (using the Cockcroft Gault equation) at Screening.
13. Has a positive urine drug or alcohol test at Screening or Check-in. A positive test result for cannabinoids may be permitted if the result to the cannabis intoxication evaluation is negative at Check-in.
14. If female, has a positive pregnancy test, is breastfeeding or lactating, or intends to become pregnant from Screening through Day 5.
15. Has been treated for depression, diabetes, asthma, emphysema, or chronic obstructive pulmonary disease within 12 months of Check-in.
16. Has previously been diagnosed with any form of cancer, except for basal cell or squamous epithelial carcinomas of the skin that have been resected.
17. Has used medications known to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, desipramine, isoniazid, ketoconazole, miconazole, phenobarbital, rifampin, tranylcypromine, methoxsalen) within 6 weeks prior to Check-in.
18. Has used a product containing pseudoephedrine within 48 hours prior to Check-in.
19. Has used any other tobacco- or nicotine-containing products other than closed-system ENDS products (e.g., open-system ENDS, cigarettes, cigars, pipes, snuff, pouches, chewing tobacco, nicotine inhalers, nicotine patches, nicotine sprays, nicotine lozenges, or nicotine gum) within 7 days of Check-in.
20. 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 Check-in.
21. Is a self-reported puffer (i.e., draws aerosol from the ENDS into the mouth and throat but does not inhale).
22. Is postponing a planned vaping quit attempt in order to participate in the study.
23. Has donated plasma within 7 days prior to Check-in.
24. Has provided a whole blood donation, had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Check-in.
25. 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 Check-in.
26. 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 or is a named party or class representative in litigation with the tobacco or ENDS industry.
27. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the clinic site(s).
28. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the Sponsor.
29. Has previously been withdrawn from or has completed this study.
30. 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: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Product Use Sequence 1; Products use sequence: Period 1 - RELX ENDS tobacco flavor Period 2 - RELX ENDS menthol flavor Period 3 - Usual Brand ENDS	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions
Experimental: Product Use Sequence 2; Products use sequence: Period 1 - RELX ENDS menthol flavor Period 2 - Usual Brand ENDS Period 3 - RELX ENDS tobacco flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions
Experimental: Product Use Sequence 3; Products use sequence: Period 1 - Usual Brand ENDS Period 2 - RELX ENDS tobacco flavor Period 3 - RELX ENDS menthol flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions
Experimental: Product Use Sequence 4; Products use sequence: Period 1 - Usual Brand ENDS Period 2 - RELX ENDS menthol flavor Period 3 - RELX ENDS tobacco flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions
Experimental: Product Use Sequence 5; Products use sequence: Period 1 - RELX ENDS tobacco flavor Period 2 - Usual Brand ENDS Period 3 - RELX ENDS menthol flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions
Experimental: Product Use Sequence 6; Products use sequence: Period 1 - RELX ENDS menthol flavor Period 2 - RELX ENDS tobacco flavor Period 3 - Usual Brand ENDS	Other: RELX ENDS Tobacco Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: Subject Usual Brand ENDS; Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine uptake	PK Session baseline-adjusted maximum plasma nicotine concentration [Cmax]	120 minutes
Nicotine uptake	PK Session baseline-adjusted area under the nicotine concentration-time curve [AUC(0-120)]	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine uptake - PK Session	PK Session baseline-adjusted area under the nicotine concentration-time curve [AUC(0-15)]	15 minutes
Nicotine uptake - PK Session	PK Session time of the maximum post-baseline nicotine concentration [Tmax]	120 minutes
Nicotine uptake - Ad Libitum Session	Ad Libitum Session baseline-adjusted area under the nicotine concentration-time curve [AUC(0-480)]	480 minutes
Subject effects as measured by the Modified Product Evaluation Scale	Subjective product assessments during the Ad Libitum Session as measured by responses to the Modified Product Evaluation Scale (scale range of 1 [not at all] to 7 [extremely])	480 minutes
Subject effects as measured by the Future Intent to Use questionnaire	Subjective product assessments during the Ad Libitum Session as measured by responses to the Future Intent to Use questionnaire (visual analog scale range of "Definitely Would Not" to "Definitely Would")	480 minutes
Subject effects as measured by the Urge to Vape questionnaire	Subjective product assessments during the PK Session as measured by responses to the Urge to Vape questionnaire (visual analog scale range of "Not at All" to "Extreme")	120 minutes
Subject effects as measured by the Product Liking questionnaire	Subjective product assessments during the PK Session as measured by responses to the Product Liking questionnaire (visual analog scale range of "Not at All" to "Extremely")	120 minutes
Physiologic effects as measured by heart rate	Heart rate measurements during the Ad Libitum Session	480 minutes
Physiologic effects as measured by heart rate	Heart rate measurements during the PK Session	120 minutes
Physiologic effects as measured by blood pressure	Blood pressure measurements during the Ad Libitum Session	480 minutes
Physiologic effects as measured by blood pressure	Blood pressure measurements during the PK Session	120 minutes
Study product use	Change in weight of study products during the Ad Libitum Session	480 minutes
Study product use	Number of requests to use the study products during the Ad Libitum Session	480 minutes
Study product use	Number of puffs taken from the study products during the Ad Libitum Session topography assessment	60 minutes
Study product use	Duration of puffs taken from the study products during the Ad Libitum Session topography assessment	60 minutes
Study product use	Volume of puffs taken from the study products during the Ad Libitum Session topography assessment	60 minutes
Study product use	Flow rate of puffs taken from the study products during the Ad Libitum Session topography assessment	60 minutes
Study product use	Inter-puff interval of puffs taken from the study products during the Ad Libitum Session topography assessment	60 minutes
Study product use	Change in weight of study products during the PK Session	5 minutes
Study product use	Number of puffs taken from the study products during the PK Session	5 minutes
Safety and tolerability	Incidence of product-use emergent adverse events	24 hours
Safety and tolerability	Incidence of product malfunction or misuse	24 hours

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): January 4, 2021
• Study Completion (Actual): January 14, 2021

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Nicotine; Electronic Nicotine Delivery System; E-cigarette; Topography; Abuse Liability
• Additional Relevant MeSH Terms: Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: RELX-002

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