A Study to Evaluate Nicotine Uptake and Biomarkers in Adult Smokers Using mybluTM Electronic Cigarettes

Study Overview
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Brief Summary
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This study evaluates the overall performance of the currently-marketed MybluTM e-cigarette device and pods, as assessed by nicotine uptake, exposure to smoke constituents, safety and consumer satisfaction, over 8 days. The study is designed as an open-label, randomized study in adult smokers. Subjects are invited to participate to a second part of the study, for 5 additional days, to compare the use of MybluTM to the use of subject's usual brand combustible cigarettes.

Official Title
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An Open-Label, Randomized, Crossover Study to Assess Nicotine Uptake, Tobacco-Related Biomarkers of Exposure, Biomarkers of Potential Harm, and Puff Topography With Use of mybluTM Electronic Cigarettes in Adult Smokers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Myblu flavor A_2.4
* Other: Myblu flavor B_2.4
* Other: Myblu flavor C_2.4
* Other: Myblu flavor D_2.4
* Other: Myblu flavor E_1.2
* Other: Myblu flavor F_1.2
* Other: Myblu flavor G_2.4
* Other: Myblu flavor H_2.4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: smoking an average of at least 10 manufactured combustible cigarettes per day for at least 12 months prior to Screening tested positive for urine cotinine (≥ 200 ng/mL) at Screening exhaled carbon monoxide > 10 ppm (parts per million) at Screening Exclusion Criteria: relevant illness history relevant medication use body mass index (BMI) > 40 kg/m2 or < 18 kg/m2 at Screening allergy to propylene glycol or glycerin use of nicotine-containing products other than manufactured combustible cigarettes within 14 days prior to Check-in use of any prescription smoking cessation treatments within 3 months prior to Check-in smokers who draw smoke from the cigarette into the mouth and throat but do not inhale planning to quit smoking during the study 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Product use sequence ABDC<br>Subjects use MybluTM e-cigarette product variant A (2.4% nicotine) ad libitum for 2 days, then switch to use variant B (2.4% nicotine) for 2 days, then D (2.4% nicotine) for 2 days and then C (2.4% nicotine) for 2 days. A washout period of 12 hours product abstinence is observed between product variants. For each product variant, in the morning of the second product use day, a controlled product use session is performed (10 puffs taken at 30-second intervals, with puffs 3 seconds in duration). | Other: Myblu flavor A_2.4<br>* Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine<br>Other: Myblu flavor B_2.4<br>* Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine<br>Other: Myblu flavor C_2.4<br>* Use of Myblu e-cigarette with flavor C at 2.4% nicotine<br>Other: Myblu flavor D_2.4<br>* Use of Myblu e-cigarette with flavor D at 2.4% nicotine<br>|
| Experimental: Product use sequence BCAD<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor A_2.4<br>* Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine<br>Other: Myblu flavor B_2.4<br>* Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine<br>Other: Myblu flavor C_2.4<br>* Use of Myblu e-cigarette with flavor C at 2.4% nicotine<br>Other: Myblu flavor D_2.4<br>* Use of Myblu e-cigarette with flavor D at 2.4% nicotine<br>|
| Experimental: Product use sequence CDBA<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor A_2.4<br>* Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine<br>Other: Myblu flavor C_2.4<br>* Use of Myblu e-cigarette with flavor C at 2.4% nicotine<br>Other: Myblu flavor D_2.4<br>* Use of Myblu e-cigarette with flavor D at 2.4% nicotine<br>|
| Experimental: Product use sequence DACB<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor A_2.4<br>* Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine<br>Other: Myblu flavor B_2.4<br>* Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine<br>Other: Myblu flavor C_2.4<br>* Use of Myblu e-cigarette with flavor C at 2.4% nicotine<br>Other: Myblu flavor D_2.4<br>* Use of Myblu e-cigarette with flavor D at 2.4% nicotine<br>|
| Experimental: Product use sequence EFHG<br>Subjects use MybluTM e-cigarette product variant E (1.2% nicotine) ad libitum for 2 days, then switch to use variant F (1.2% nicotine) for 2 days, then H (2.4% nicotine) for 2 days and then G (2.4% nicotine) for 2 days. A washout period of 12 hours product abstinence is observed between product variants. For each product variant, in the morning of the second product use day, a controlled product use session is performed (10 puffs taken at 30-second intervals, with puffs 3 seconds in duration). | Other: Myblu flavor E_1.2<br>* Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine<br>Other: Myblu flavor F_1.2<br>* Fse of Myblu e-cigarette with flavor F at 1.2% nicotine<br>Other: Myblu flavor G_2.4<br>* Use of Myblu e-cigarette with flavor G at 2.4% nicotine<br>Other: Myblu flavor H_2.4<br>* Use of Myblu e-cigarette with flavor H at 2.4% nicotine<br>|
| Experimental: Product use sequence FGEH<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor E_1.2<br>* Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine<br>Other: Myblu flavor F_1.2<br>* Fse of Myblu e-cigarette with flavor F at 1.2% nicotine<br>Other: Myblu flavor G_2.4<br>* Use of Myblu e-cigarette with flavor G at 2.4% nicotine<br>Other: Myblu flavor H_2.4<br>* Use of Myblu e-cigarette with flavor H at 2.4% nicotine<br>|
| Experimental: Product use sequence GHFE<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor E_1.2<br>* Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine<br>Other: Myblu flavor F_1.2<br>* Fse of Myblu e-cigarette with flavor F at 1.2% nicotine<br>Other: Myblu flavor G_2.4<br>* Use of Myblu e-cigarette with flavor G at 2.4% nicotine<br>Other: Myblu flavor H_2.4<br>* Use of Myblu e-cigarette with flavor H at 2.4% nicotine<br>|
| Experimental: Product use sequence HEGF<br>Same as previous arm, but in a different randomization order. | Other: Myblu flavor E_1.2<br>* Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine<br>Other: Myblu flavor F_1.2<br>* Fse of Myblu e-cigarette with flavor F at 1.2% nicotine<br>Other: Myblu flavor G_2.4<br>* Use of Myblu e-cigarette with flavor G at 2.4% nicotine<br>Other: Myblu flavor H_2.4<br>* Use of Myblu e-cigarette with flavor H at 2.4% nicotine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Nicotine Concentration in Blood | Maximum nicotine concentration in blood (Cmax) | 180 minutes following the start of the controlled product use session on Day 2 (12 measurements over the period) | 
| Concentration of Carboxyhemoglobin in Blood | Change from baseline in the concentration of carboxyhemoglobin (COHb) in whole blood. | Baseline and 8 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 (NNK), excreted in urine during 24 hours (creatinine adjusted). | Baseline and 8 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 during 24 hours (creatinine adjusted). | Baseline and 8 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 during 24 hours (creatinine adjusted). | Baseline and 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of White Blood Cells | The change from baseline in the level of white blood cells, a biomarker of potential harm. | Baseline and 8 days | 
| Spirometry: Forced Expiratory Volume in 1 Second | The percent-predicted forced expiratory volume in 1 second (FEV1) measurement conducted in accordance with the 2005 American Thoracic Society / European Respiratory Society Joint Task Force on the standardization of spirometry, with subject in a sitting position following at least 15 minutes of rest and at least 1 hour from the last product use. | Baseline and 8 days | 
| Spirometry: Forced Vital Capacity | The percent-predicted forced vital capacity (FVC) measurement conducted in accordance with the 2005 American Thoracic Society / European Respiratory Society Joint Task Force on the standardization of spirometry, with subject in a sitting position following at least 15 minutes of rest and at least 1 hour from the last product use. | Baseline and 8 days | 
| Subjective Measure: Urge to Smoke | Urge to smoke score: Subjects answer the following question How strong is your urge to smoke right now? using a visual analogue scale. The scale ranges from Not at all, given a score of 0, to Extremely, given a score of 100, after ad libitum use of the product. | 8 days |