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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Electronic Cigarette Use

Intervention / Treatment
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* Other: RELX ENDS Tobacco Flavor
* Other: RELX ENDS Menthol Flavor
* Other: Subject Usual Brand ENDS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides voluntary consent to participate in the study as documented on the signed informed consent form (ICF). Is 22 to 59 years of age, inclusive, at the time of consent. 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. Reports weekly use of at least 3 mL of e-liquid from an ENDS product at Screening. Has a urine cotinine concentration ≥ of 200 ng/mL at Screening and Check-in. Has an exhaled carbon monoxide (ECO) concentration < 10 ppm at Check-in. 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). Is willing to comply with the requirements of the study. Exclusion Criteria: 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. Has a clinically significant abnormal finding on the physical examination, medical history, vital signs, ECG, or clinical laboratory results. Has a positive test for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen, or Hepatitis C Antibody. Has had an acute illness (e.g., upper respiratory infection, viral infection) within 14 days prior to Check-in. Has a fever (> 100.5°F) at Screening or Check-in. Has a positive COVID-19 test during the screening period, prior to Check-in. Has a body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening. Has a history of drug or alcohol abuse within 12 months of Screening. 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. Is allergic to or intolerant of components of the product e-liquid, including but not limited to, menthol, propylene glycol or glycerin. Is unable to use the CReSS topography device with the vaping device during the training session on Day -1. Has an estimated creatinine clearance < 70 mL/minute (using the Cockcroft Gault equation) at Screening. 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. If female, has a positive pregnancy test, is breastfeeding or lactating, or intends to become pregnant from Screening through Day 5. Has been treated for depression, diabetes, asthma, emphysema, or chronic obstructive pulmonary disease within 12 months of Check-in. Has previously been diagnosed with any form of cancer, except for basal cell or squamous epithelial carcinomas of the skin that have been resected. 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. Has used a product containing pseudoephedrine within 48 hours prior to Check-in. 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. 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. Is a self-reported puffer (i.e., draws aerosol from the ENDS into the mouth and throat but does not inhale). Is postponing a planned vaping quit attempt in order to participate in the study. Has donated plasma within 7 days prior to Check-in. 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. 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. 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. Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the clinic site(s). Is or has a first-degree relative (e.g., spouse, parent, sibling, child) who is a current employee of the Sponsor. Has previously been withdrawn from or has completed this study. In the opinion of an Investigator, the subject should not participate in this study.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Product Use Sequence 1<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|
| Experimental: Product Use Sequence 2<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|
| Experimental: Product Use Sequence 3<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|
| Experimental: Product Use Sequence 4<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|
| Experimental: Product Use Sequence 5<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|
| Experimental: Product Use Sequence 6<br>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<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: RELX ENDS Menthol Flavor<br>* Ad libitum use of the RELX ENDS tobacco flavor product during 8-hour and 5-minute use sessions<br>Other: Subject Usual Brand ENDS<br>* Ad libitum use of the usual brand product during 8-hour and 5-minute use sessions<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine, Electronic Nicotine Delivery System, Pharmacokinetics, Abuse Liability, Topography, E-cigarette