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

• Sponsor: Fontem Ventures BV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04019626
• Collaborator: (none)
• Enrollment: 240
• Location: 1
• Arms: 6
• Actual Duration (Months): 22
• Patients Per Site Per Month: 10.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	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%	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: Mar 1, 2019
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Continue-smoking The subject's usual brand of combustible cigarette	Other: Continue-smoking; Ad-libitum use of subjects' usual brand combustible cigarette
Experimental: myblu Tobacco 2.5% 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%; Ad-libitum use of myblu e-cigarette with Tobacco flavor 2.5% nicotine
Experimental: myblu Tobacco 4.0% 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%; Ad-libitum use of myblu e-cigarette with Tobacco flavor 4.0% nicotine
Experimental: myblu Honeymoon 2.5% 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%; Ad-libitum use of myblu e-cigarette with Honeymoon flavor 2.5% nicotine
Experimental: myblu Honeymoon 4.0% 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%; Ad-libitum use of myblu e-cigarette with Honeymoon flavor 4.0% nicotine
Active Comparator: JUUL 5% JUUL® system with Virginia Tobacco Flavor JUULpod, 5.0% nicotine. This arm is only included in the PK sub-study.	Other: JUUL 5%; Ad-libitum use of JUUL 5% e-cigarette

Outcome Measures

Primary Outcome Measures

1. Concentration of Carboxyhemoglobin in Blood [Baseline and 56 days]

   Change from baseline in the % saturation of carboxyhemoglobin (COHb) in whole blood

2. Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours [Baseline and 56 days]

   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

3. Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours [Baseline and 56 days]

   Change from baseline in the amount of 3-hydroxypropylmercapturic acid (3-HPMA - a biomarker of exposure to acrolein) excreted in urine in 24-hours

4. Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours [Baseline and 56 days]

   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

Secondary Outcome Measures

1. Amount of Nicotine Equivalents in Urine in 24 Hours [Baseline and 56 days]

   The change from baseline in the amount of nicotine equivalents excreted in urine in 24-hours

2. Level of White Blood Cells [Baseline and 56 days]

   The change from baseline in the level of white blood cells, which is a biomarker of potential harm

3. Subjective Measure: Nicotine Withdrawal Symptoms Total Score [56 days]

   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.

4. Maximum Nicotine Concentration in Blood [5 minutes prior, and at 3, 5, 7, 10, 12, 15, 20, 30, 60, 120 and 180 minutes post dose]

   The maximum nicotine concentration in blood (Cmax)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Fontem Ventures BV

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 24, 2020
• Statistical Analysis Plan - Mar 5, 2020

More Information

Publications

None provided.

• Responsible Party: Fontem Ventures BV
• ClinicalTrials.gov Identifier: NCT04019626
• Other Study ID Numbers: CA22747
• First Posted: Jul 15, 2019
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking	JUUL 5%
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette	Use of JUUL 5% nicotine e-cigarette
Period Title: Overall Study
STARTED	42	42	45	46	44	21
COMPLETED	36	32	37	39	38	20
NOT COMPLETED	6	10	8	7	6	1

Baseline Characteristics

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking	Total
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette	Total of all reporting groups
Overall Participants	42	42	45	46	44	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.9 (11.72)	37.8 (10.47)	40.3 (9.43)	40.3 (9.75)	39.7 (10.44)	39.6 (10.32)
Sex: Female, Male (Count of Participants)
Female	14 33.3%	14 33.3%	18 40%	20 43.5%	18 40.9%	84 38.4%
Male	28 66.7%	28 66.7%	27 60%	26 56.5%	26 59.1%	135 61.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 2.2%	0 0%	1 0.5%
Asian	1 2.4%	1 2.4%	0 0%	0 0%	0 0%	2 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 2.2%	0 0%	1 0.5%
Black or African American	12 28.6%	16 38.1%	18 40%	16 34.8%	13 29.5%	75 34.2%
White	27 64.3%	23 54.8%	24 53.3%	27 58.7%	30 68.2%	131 59.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.8%	2 4.8%	3 6.7%	1 2.2%	1 2.3%	9 4.1%
Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.0 (4.7)	30.0 (4.9)	28.9 (4.7)	28.9 (5.2)	29.9 (5.6)	29.1 (5.1)
Blood carboxyhemoglobin (COHb) % (% saturation) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% saturation]	4.9 (2.2)	4.8 (1.8)	4.8 (2.1)	5.3 (1.9)	5.7 (2.0)	5.1 (2.0)
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) amount excreted in urine (ng/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/24 hours]	411.0 (333.2)	406.8 (328.8)	410.4 (351.2)	479.4 (404.2)	513.7 (403.7)	444.26 (346.2)
3-hydroxypropylmercapturic acid (3-HPMA) amount excreted in urine (ug/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ug/24 hours]	1592.5 (818.2)	1730.3 (1044.2)	1749.7 (780.1)	1919.0 (999.8)	2214.0 (1172.6)	1841.1 (963.0)
S-phenyl mercapturic acid (S-PMA) amount excreted in urine (ug/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ug/24 hours]	5.3 (3.7)	5.9 (4.3)	6.5 (5.1)	7.2 (5.2)	8.6 (5.9)	6.7 (4.8)
Nicotine equivalents amount excreted in urine (mg/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/24 hours]	13.6 (6.8)	14.1 (7.5)	17.1 (13.3)	16.2 (6.5)	18.0 (7.3)	15.8 (8.3)
Level of white blood cells (cells*thousands/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells*thousands/uL]	7.7 (2.0)	7.0 (2.0)	6.8 (1.8)	7.4 (2.0)	7.2 (2.2)	7.2 (2.0)

Outcome Measures

1. Primary Outcome

Title	Concentration of Carboxyhemoglobin in Blood
Description	Change from baseline in the % saturation of carboxyhemoglobin (COHb) in whole blood
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (cf "Study Description"). Therefore, the number of subjects analysed in one arm may be different from the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	32	49	24	33	37
Mean (Standard Deviation) [% change from baseline]	-59.6 (23.3)	-62.7 (19.4)	-46.4 (35.1)	-62.7 (21.2)	8.5 (28.3)

2. Primary Outcome

Title	Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours
Description	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
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	32	52	25	35	38
Mean (Standard Deviation) [% change from baseline]	-58.3 (72.8)	-44.7 (150.5)	-62.7 (36.2)	-70.7 (33.7)	1.1 (29.6)

3. Primary Outcome

Title	Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours
Description	Change from baseline in the amount of 3-hydroxypropylmercapturic acid (3-HPMA - a biomarker of exposure to acrolein) excreted in urine in 24-hours
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	32	52	25	35	38
Mean (Standard Deviation) [% change from baseline]	-60.0 (28.2)	-55.7 (46.1)	-50.5 (36.2)	-53.8 (64.5)	1.6 (40.6)

4. Primary Outcome

Title	Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours
Description	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
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	32	52	25	35	38
Mean (Standard Deviation) [% change from baseline]	-85.9 (32.5)	-44.9 (257.5)	-63.1 (79.3)	-73.8 (55.7)	-2.7 (38.4)

5. Secondary Outcome

Title	Amount of Nicotine Equivalents in Urine in 24 Hours
Description	The change from baseline in the amount of nicotine equivalents excreted in urine in 24-hours
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	32	51	24	35	38
Mean (Standard Deviation) [% change from baseline]	-7.8 (74.0)	16.6 (61.1)	-13.8 (54.5)	-1.3 (38.8)	-7.0 (27.0)

6. Secondary Outcome

Title	Level of White Blood Cells
Description	The change from baseline in the level of white blood cells, which is a biomarker of potential harm
Time Frame	Baseline and 56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	31	51	25	35	37
Mean (Standard Deviation) [% change from baseline]	-9.2 (16.7)	-4.3 (16.8)	-8.7 (17.9)	-8.5 (16.3)	4.7 (17.0)

7. Secondary Outcome

Title	Subjective Measure: Nicotine Withdrawal Symptoms Total Score
Description	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.
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

Available data from the Intent-to-treat population (ITT; randomized subjects in the main study with at least one documented product-use experience from Day 1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects analysed in one arm may be different than the number of subjects who were initially assigned to this product at the study start. JUUL arm was only for PK sub-study

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette
Measure Participants	31	51	26	33	38
Mean (Standard Deviation) [score on a scale]	8.6 (6.7)	5.7 (5.5)	7.1 (5.3)	6.8 (5.8)	8.1 (5.9)

8. Secondary Outcome

Title	Maximum Nicotine Concentration in Blood
Description	The maximum nicotine concentration in blood (Cmax)
Time Frame	5 minutes prior, and at 3, 5, 7, 10, 12, 15, 20, 30, 60, 120 and 180 minutes post dose

Outcome Measure Data

Analysis Population Description

Sub-group of participants who participated in the PK sub-study, on Day 1

Arm/Group Title	Myblu Tobacco Flavor 2.5%	Myblu Tobacco Flavor 4.0%	Myblu Honeymoon 2.5%	Myblu Honeymoon 4.0%	Continue-smoking	JUUL® 5.0%
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine	Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine	Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine	The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette	Use of JUUL® system with Virginia Tobacco Flavor JUULPod, 5.0% nicotine
Measure Participants	20	19	19	22	24	19
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4.0 (196.3)	7.3 (118.6)	4.3 (191.3)	8.9 (159.8)	13.5 (62.5)	6.9 (160.1)

Adverse Events

Time Frame	72 days (58 study days plus 14 follow-up days) for all arms except JUUL. 15 day for JUUL arm.
Adverse Event Reporting Description	Adverse events of the Safety Population (all subjects with at least one reported product use from Day -1) is presented. Subjects using the myblu e-cigarette were allowed to switch product variant in the course of the study (see "Study Description"). Therefore, the number of subjects at risk in one arm may be different than the number of subjects who were initially assigned to this product at the study start.
Arm/Group Title	Myblu Tobacco Flavor 2.5%		Myblu Tobacco Flavor 4.0%		Myblu Honeymoon 2.5%		Myblu Honeymoon 4.0%		Continue-smoking		JUUL® 5.0%
Arm/Group Description	Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine		Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine		Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine		Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine		The subject's usual brand of combustible cigarette Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette		Use of JUUL® system with Virginia Tobacco Flavor JUULPod, 5.0% nicotine
All Cause Mortality
	Myblu Tobacco Flavor 2.5%		Myblu Tobacco Flavor 4.0%		Myblu Honeymoon 2.5%		Myblu Honeymoon 4.0%		Continue-smoking		JUUL® 5.0%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/71 (0%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		0/21 (0%)
Serious Adverse Events
	Myblu Tobacco Flavor 2.5%		Myblu Tobacco Flavor 4.0%		Myblu Honeymoon 2.5%		Myblu Honeymoon 4.0%		Continue-smoking		JUUL® 5.0%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/71 (0%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Myblu Tobacco Flavor 2.5%		Myblu Tobacco Flavor 4.0%		Myblu Honeymoon 2.5%		Myblu Honeymoon 4.0%		Continue-smoking		JUUL® 5.0%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/55 (14.5%)		10/71 (14.1%)		6/47 (12.8%)		6/57 (10.5%)		7/44 (15.9%)		8/21 (38.1%)
Gastrointestinal disorders
Diarrhoea	3/55 (5.5%)		1/71 (1.4%)		0/47 (0%)	0	0/57 (0%)	0	0/44 (0%)	0	0/21 (0%)	0
Dyspepsia	1/55 (1.8%)		0/71 (0%)		0/47 (0%)		0/57 (0%)		2/44 (4.5%)		0/21 (0%)
Nausea	1/55 (1.8%)		1/71 (1.4%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		1/21 (4.8%)
Infections and infestations
Upper respiratory tract infection	0/55 (0%)		0/71 (0%)		2/47 (4.3%)		2/57 (3.5%)		0/44 (0%)		4/21 (19%)
Urinary tract infection	0/55 (0%)		0/71 (0%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		1/21 (4.8%)
Injury, poisoning and procedural complications
Laceration	0/55 (0%)		2/71 (2.8%)		0/47 (0%)		0/57 (0%)		1/44 (2.3%)		0/21 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/55 (0%)		0/71 (0%)		0/47 (0%)		2/57 (3.5%)		0/44 (0%)		0/21 (0%)
Nervous system disorders
Dizziness	0/55 (0%)		3/71 (4.2%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		0/21 (0%)
Headache	0/55 (0%)		1/71 (1.4%)		4/47 (8.5%)		2/57 (3.5%)		4/44 (9.1%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/55 (5.5%)		2/71 (2.8%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		1/21 (4.8%)
Hiccups	0/55 (0%)		0/71 (0%)		0/47 (0%)		0/57 (0%)		0/44 (0%)		1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.