A Study to Assess Tobacco-related Biomarkers of Exposure in Smokers Using myBlu E-cigarettes

Study Overview
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Brief Summary
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The purpose of this study is to assess changes in exposure to selected harmful and potentially harmful substances related to tobacco/nicotine use when adult smokers switch from their usual brand of combustible cigarettes to the myblu e-cigarette, for up to 56 days. This study is designed as an open-label, partially-randomized, parallel-arm, multi-site study in healthy adult smokers. Some subjects will be selected to take part in additional procedures as part of a pharmacokinetics (PK) sub-study.

Detailed Description
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Subjects are randomized to either continue smoking conventional cigarettes, or switch to use the myblu e-cigarette. Within the myblu arm, subjects were assigned to one of four variants of the myblu e-cigarette, having different flavors and nicotine strengths. Initial product assignment for each subject was based on preference as a method to enhance compliance. To further improve compliance through Day 56, subjects may have been allowed to choose to switch to another variant of the myblu e-cigarette, or to continue using the same e-liquid selected initially.

Official Title
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An Open-label, Parallel Study to Assess Tobacco-related Biomarkers of Exposure, Biomarkers of Potential Harm, and Nicotine Uptake During a 56-day Switch to Myblu E-cigarettes in Adult Smokers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Continue-smoking
* Other: myblu Tobacco 2.5%
* Other: myblu Tobacco 4.0%
* Other: myblu Honeymoon 2.5%
* Other: myblu Honeymoon 4.0%
* Other: JUUL 5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having smoked ≥5 manufactured combustible cigarettes per day for at least one year Exhaled carbon monoxide level of >10 ppm at screening Tested positive for urinary cotinine (approximately 200 ng/mL) at screening Exclusion Criteria: Relevant illness history Relevant medication use Body mass index (BMI) of less than 18 kg/m2 or greater than 40 kg/m2 Allergy to propylene glycol or glycerin Use of nicotine-containing products other than manufactured cigarettes Use of prescription smoking cessation treatments Smokers who draw smoke into their mouth and throat but do not inhale Intent or desire to stop smoking Female subjects who are pregnant, lactating, or intend to become pregnant

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 |
| --- | --- |
| Active Comparator: Continue-smoking<br>The subject's usual brand of combustible cigarette | Other: Continue-smoking<br>* Ad-libitum use of subjects' usual brand combustible cigarette<br>|
| Experimental: myblu Tobacco 2.5%<br>myblu e-cigarette system with Tobacco flavor, 2.5% nicotine. At Day 28 of the study, subjects may be allowed to switch to another myblu variant. | Other: myblu Tobacco 2.5%<br>* Ad-libitum use of myblu e-cigarette with Tobacco flavor 2.5% nicotine<br>|
| Experimental: myblu Tobacco 4.0%<br>myblu e-cigarette system with Tobacco flavor, 4.0% nicotine. At Day 28 of the study, subjects may be allowed to switch to another myblu variant. | Other: myblu Tobacco 4.0%<br>* Ad-libitum use of myblu e-cigarette with Tobacco flavor 4.0% nicotine<br>|
| Experimental: myblu Honeymoon 2.5%<br>myblu e-cigarette system with Honeymoon flavor, 2.5% nicotine. At Day 28 of the study, subjects may be allowed to switch to another myblu variant. | Other: myblu Honeymoon 2.5%<br>* Ad-libitum use of myblu e-cigarette with Honeymoon flavor 2.5% nicotine<br>|
| Experimental: myblu Honeymoon 4.0%<br>myblu e-cigarette system with Honeymoon flavor, 4.0% nicotine. At Day 28 of the study, subjects may be allowed to switch to another myblu variant. | Other: myblu Honeymoon 4.0%<br>* Ad-libitum use of myblu e-cigarette with Honeymoon flavor 4.0% nicotine<br>|
| Active Comparator: JUUL 5%<br>JUUL® system with Virginia Tobacco Flavor JUULpod, 5.0% nicotine. This arm is only included in the PK sub-study. | Other: JUUL 5%<br>* Ad-libitum use of JUUL 5% e-cigarette<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Carboxyhemoglobin in Blood | Change from baseline in the % saturation of carboxyhemoglobin (COHb) in whole blood | Baseline and 56 days | 
| Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | Change from baseline in the amount of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL - a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) excreted in urine in 24-hours | Baseline and 56 days | 
| Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | Change from baseline in the amount of 3-hydroxypropylmercapturic acid (3-HPMA - a biomarker of exposure to acrolein) excreted in urine in 24-hours | Baseline and 56 days | 
| Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | Change from baseline in the amount of s-phenyl mercapturic acid (S-PMA - a biomarker of exposure to benzene) excreted in urine in 24-hours | Baseline and 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Nicotine Equivalents in Urine in 24 Hours | The change from baseline in the amount of nicotine equivalents excreted in urine in 24-hours | Baseline and 56 days | 
| Level of White Blood Cells | The change from baseline in the level of white blood cells, which is a biomarker of potential harm | Baseline and 56 days | 
| Subjective Measure: Nicotine Withdrawal Symptoms Total Score | Nicotine withdrawal symptoms are measured using the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R) questionnaire. The DSM-5 and craving items from the MTWS-R have been included. The subjects rate themselves on the questionnaire, which includes symptoms such as angry, irritable, frustrated, depressed mood, restless, insomnia. Each question is rated from 0 (none) to 4 (severe). Total scores may range from 0 to a maximum of 32. | 56 days | 
| Maximum Nicotine Concentration in Blood | The maximum nicotine concentration in blood (Cmax) | 5 minutes prior, and at 3, 5, 7, 10, 12, 15, 20, 30, 60, 120 and 180 minutes post dose |