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

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

This study is being conducted to evaluate nicotine uptake and exposure, the 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 smokers.

Study Overview

• Status: Completed
• Conditions: Electronic Cigarette Use
• Intervention / Treatment: Other: RELX ENDS Tobacco Flavor; Other: RELX ENDS Menthol Flavor; Other: Usual Brand Cigarette; Other: Nicorette White Ice Mint nicotine polacrilex gum

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • 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 smoker for at least 12 months prior to Screening and through check-in. Brief periods of non-smoking (e.g., up to ~7 consecutive days due to illness, trying to quit, participation in a study where smoking was prohibited) ≥ 30 days prior to Screening will be permitted at the discretion of the Investigator.
4. Reports typically smoking 10 combustible cigarettes (king size or 100s) per day at Screening.
5. Has a urine cotinine concentration ≥ 200 ng/mL at Screening and Check-in.
6. Has an exhaled carbon monoxide (ECO) concentration > 10 ppm at Screening and 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.
8. 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).
9. 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 (HBsAg) or Hepatitis C Antibody (HCVAb).
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 (BMI) 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 (CYP) 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 an ENDS product on more than 5 days within 3 months prior to Screening and through Check-in.
20. Reports use of a very-low nicotine content cigarette (e.g., Moonlight, Spectrum, VLN) as usual brand.
21. Has used any tobacco- or nicotine-containing products other than manufactured cigarettes (e.g., ENDS, roll-your-own cigarettes, bidis, snuff, pouches, pipes, cigars, chewing tobacco, nicotine inhalers, nicotine patches, nicotine sprays, nicotine lozenges, or nicotine gum) within 7 days of Check-in.
22. Has used any products for the purpose of smoking cessation, including, but not limited to, nicotine replacement therapies, varenicline (Chantix), or buproprion (Zyban) from 30 days prior to Screening through Check-in.
23. Is a self-reported puffer (i.e., draws smoke from the cigarette into the mouth and throat but does not inhale).
24. Is postponing a planned smoking quit attempt in order to participate in the study.
25. Has donated plasma within 7 days prior to Check-in.
26. 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.
27. 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 drug (whichever is longer) prior to Check-in.
28. 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.
29. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the clinic site.
30. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the Sponsor.
31. Has previously been withdrawn from or has completed this study.
32. In the opinion of the 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Product Use Sequence 1; Period 1 - RELX ENDS Tobacco Flavor Period 2 - RELX ENDS Menthol Flavor Period 3 - Nicorette White Ice Mint Nicotine Polacrilex Gum Period 4 - Usual Brand Cigarette	Other: RELX ENDS Tobacco Flavor; Ad libitum use of RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of RELX ENDS Menthol flavor product during 8-hour and 5-minute use sessions; Other: Usual Brand Cigarette; Ad libitum use of subjects usual brand product during 8-hour and single cigarette use sessions; Other: Nicorette White Ice Mint nicotine polacrilex gum; Ad libitum use of Nicorette White Ice Mint nicotine polacrilex gum product during 8-hour and 30-minute use sessions
Experimental: Product Use Sequence 2; Period 1 - RELX ENDS Menthol Flavor Period 2 - Usual Brand Cigarette Period 3 - RELX ENDS Tobacco Flavor Period 4 - Nicorette White Ice Mint Nicotine Polacrilex Gum	Other: RELX ENDS Tobacco Flavor; Ad libitum use of RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of RELX ENDS Menthol flavor product during 8-hour and 5-minute use sessions; Other: Usual Brand Cigarette; Ad libitum use of subjects usual brand product during 8-hour and single cigarette use sessions; Other: Nicorette White Ice Mint nicotine polacrilex gum; Ad libitum use of Nicorette White Ice Mint nicotine polacrilex gum product during 8-hour and 30-minute use sessions
Experimental: Product Use Sequence 3; Period 1 - Usual Brand Cigarette Period 2 - Nicorette White Ice Mint Nicotine Polacrilex Gum Period 3 - RELX ENDS Menthol Flavor Period 4 - RELX ENDS Tobacco Flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of RELX ENDS Menthol flavor product during 8-hour and 5-minute use sessions; Other: Usual Brand Cigarette; Ad libitum use of subjects usual brand product during 8-hour and single cigarette use sessions; Other: Nicorette White Ice Mint nicotine polacrilex gum; Ad libitum use of Nicorette White Ice Mint nicotine polacrilex gum product during 8-hour and 30-minute use sessions
Experimental: Product Use Sequence 4; Period 1 - Nicorette White Ice Mint Nicotine Polacrilex Gum Period 2 - RELX ENDS Tobacco Flavor Period 3 - Usual Brand Cigarette Period 4 - RELX ENDS Menthol Flavor	Other: RELX ENDS Tobacco Flavor; Ad libitum use of RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions; Other: RELX ENDS Menthol Flavor; Ad libitum use of RELX ENDS Menthol flavor product during 8-hour and 5-minute use sessions; Other: Usual Brand Cigarette; Ad libitum use of subjects usual brand product during 8-hour and single cigarette use sessions; Other: Nicorette White Ice Mint nicotine polacrilex gum; Ad libitum use of Nicorette White Ice Mint nicotine polacrilex gum product during 8-hour and 30-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
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
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
Subjective 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
Subjective 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 annalog scale range of "Definitely Would Not" to " Definitely Would")	480 minutes
Subjective Effects as measured by the Urge to Smoke questionnaire	Subjective product assessments during the PK Session as measured by responses to the Urge to Smoke questionnaire (visual analog scale range of "Not at All" to "Extreme")	120 minutes
Subjective 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
Carbon Monoxide Exposure	Change in exhaled carbon monoxide during the PK Session	25 minutes (50 minutes for the nicotine gum period)
Study Product Use	Change in weight of the RELX 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 (requests to use the RELX ENDS product, number of cigarettes smoked, number of pieces of gum used)	480 minutes
Study Product Use	Number of puffs taken from the RELX ENDS and cigarette during the Ad Libitum Session topography assessment	60 minutes
Study Product Use	Duration of puffs taken from the RELX ENDS and cigarette during the Ad Libitum Session topography assessment	60 minutes
Study Product Use	Volume of puffs taken from the RELX ENDS and cigarette during the Ad Libitum Session topography assessment	60 minutes
Study Product Use	Flow rate of puffs taken from the RELX ENDS and cigarette during the Ad Libitum Session topography assessment	60 minutes
Study Product Use	Inter-puff interval of puffs taken from the RELX ENDS and cigarette during the Ad Libitum Session topography assessment	60 minutes
Study Product Use	Pre- to post-use RELX pod weight difference during the PK Session	5 minutes
Study Product Use	Number of puffs from the RELX ENDS and cigarettes during the PK Session	5 minutes
Incidence of product-use emergent adverse events [Safety and Tolerability]	Incidence of product-use emergent adverse events	24 hours
Incidence of product malfunction or misuse of the RELX ENDS [Safety and Tolerability]	Incidence of product malfunction or misuse of the RELX ENDS	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): November 3, 2020
• Primary Completion (Actual): March 12, 2021
• Study Completion (Actual): March 19, 2021

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 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: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Dermatologic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antipruritics; Nicotine; Menthol
• Other Study ID Numbers: RELX-001

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