Identify Biomarkers of Tobacco Exposure and Nicotine Uptake From JUUL 5% in Adult Smokers

Study Overview
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Brief Summary
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The JUUL 5% Electronic Nicotine Delivery System (ENDS) is being studied as an alternative to combustible cigarette use. This study aims to find out how much nicotine is in the blood and urine of healthy adult subjects after using three JUUL 5% ENDS compared to smoking usual brands of combustible cigarettes and stopping smoking.

Detailed Description
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This study will serve as a clinical evaluation of the exclusive use of selected JUUL ENDS, with the purpose of gaining an understanding of toxicant exposure.

Official Title
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A Randomized, Open-Label, Parallel-Group Study to Characterize Biomarkers of Tobacco Exposure and Nicotine Uptake From JUUL 5% Electronic Nicotine Delivery Systems (ENDS) in Adult Smokers

Conditions
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Nicotine Dependence, Other Tobacco Product, Tobacco Use, Smoking, Tobacco

Intervention / Treatment
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* Other: Treatment with JUUL 5%, Virginia Tobacco
* Other: Treatment with JUUL 5%, Cool Mint, ENDS
* Other: Treatment with JUUL 5%, Mango, ENDS
* Other: JUUL 5%, Creme Bruele, ENDS
* Other: Combustible cigarette
* Other: Smoking Cessation


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy, adult, male or female smoker, 21 to 65 years of age. Has been a smoker for at least 12 months prior to Screening. Currently smokes an average of 10 cigarettes each day. Has a positive urine cotinine (≥ 500 ng/mL). Has an exhaled carbon monoxide (CO) > 12 ppm. A female subject of childbearing potential must have been using contraception and agree to continue using it through completion of the study: Provides voluntary consent to participate in this study documented on the signed informed consent form (ICF). Key Exclusion Criteria Has a history or presence of clinically significant conditions. Has a body mass index (BMI) > 40 kg/m2 or < 18 kg/m2 at Screen Has a history of drug or alcohol abuse Has an estimated creatinine clearance < 80 mL/minute If female, the subject is pregnant, lactating, or intends to become pregnant during the time period from Screening through the end of study. Has used nicotine-containing products other than manufactured cigarettes within 14days of screening. Is planning to quit smoking during the study, planning to quit within 3 months following Day 1

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with JUUL 5%, Virginia Tobacco<br>JUUL 5%,Virginia Tobacco [5 days] in confinement. | Other: Treatment with JUUL 5%, Virginia Tobacco<br>* JUUL 5%, ENDS for 5-days in confinement<br>* Other names: JUUL;|
| Experimental: Treatment with JUUL 5%, Cool Mint, ENDS<br>JUUL 5%, Cool Mint [5 days] in confinement. | Other: Treatment with JUUL 5%, Cool Mint, ENDS<br>* JUUL 5%, ENDS for 5-days in confinement<br>* Other names: JUUL;|
| Experimental: Treatment with JUUL 5%, Mango, ENDS<br>JUUL 5%, Mango [5 days] in confinement. | Other: Treatment with JUUL 5%, Mango, ENDS<br>* JUUL 5%, ENDS for 5-days in confinement<br>* Other names: JUUL;|
| Experimental: JUUL 5%, Creme Bruele, ENDS<br>JUUL 5%, Creme Bruele [5 days] in confinement. | Other: JUUL 5%, Creme Bruele, ENDS<br>* JUUL 5%, ENDS for 5-days in confinement<br>* Other names: JUUL;|
| Active Comparator: Combustible cigarette<br>Exclusive use of combustible cigarette [5 days] in confinement. | Other: Combustible cigarette<br>* Exclusive use of combustible cigarette for 5 days in confinement.<br>|
| Sham Comparator: Smoking cessation (no smoking)<br>Smoking cessation (no smoking). | Other: Smoking Cessation<br>* No smoking for 5-days in confinement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in primary biomarkers day 5 values for each JUUL 5% product will be compared to baseline: | Change in ; Urine N nitrosonornicotine (NNN), 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), 3 hydroxypropylmercapturic acid (3-HPMA), monohydroxybutenylmercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) Blood carboxyhemoglobin (COHb) | [Time Frame: 5 days] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of 2-cyanoethyl-mercapturic acid (CEMA) in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of 1-hydroxypyrene (1-OHP) in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of Nicotine in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of Cotinine in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of trans-3'-hydroxycotinine in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of Glucuronides in urine | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of Nicotine in blood | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of Cotinine in blood | Change in Biomarker | [Time Frame: 5 days] | 
| Change in concentration of trans-3'-hydroxycotinine in blood | Change in Biomarker | [Time Frame: 5 days | 
| Change in maximum concentration (Cmax) Plasma pharmacokinetic (PK) of Nicotine | Nicotine absorption | [Time Frame: Day 7, | 
| Change in time to maximum concentration (Tmax) Plasma PK of Nicotine | Nicotine absorption | [Time Frame: Day 7, | 
| Change of area under the curve (AUC) Plasma PK of Nicotine | Nicotine absorption | [Time Frame: Day 7, | 
| Product use over 5-day period and during 5-minute fixed and ad libitum use episodes | Change in product use | [Time Frame: 7 days] | 
| Measure of subjective Smoking Urge Assessment | Change in Assessment | [Time Frame: 6-7 days, intervention dependent] | 
| Measure of subjective product evaluation using the modified Product Evaluation Scale (mPES) | Change in Evaluation; Scale: 1 = not at all, 2 = very little, 3 = a little, 4 = moderately, 5 = a lot, 6 = quite a lot, 7 = extremely Four multi-item subscales will be derived from Satisfaction (items 1, 2, 3, and 12); Psychological Reward (items 4 through 8); Aversion (items 9, 10, 16, and 18); and Relief (item 11, 13, 14, 15, and reversed for item 19) and single items 17 and 20 will be summarized. | [Time Frame: 6-7 days, intervention dependent] | 
| Measure of future intent to use JUUL 5% Device device relative to usual combustible cigarette and smoking cessation. | Change in Intent | [Time Frame: 6-7 days, intervention dependent] | 
| Number of participants with Adverse Events associated with use of JUUL 5% Device to combustible cigarette and smoking cessation | Safety | [Time Frame: 13-14 days, intervention dependent] | 
| Incidence of JUUL 5% Device, including malfunction and/or misuse | Device performance | [Time Frame: 7 days] |