Healthy Volunteers
Conditions
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.
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.
Interventions
OTHERContinue-smoking
Ad-libitum use of subjects' usual brand combustible cigarette
OTHERmyblu Tobacco 2.5%
Ad-libitum use of myblu e-cigarette with Tobacco flavor 2.5% nicotine
OTHERmyblu Tobacco 4.0%
Ad-libitum use of myblu e-cigarette with Tobacco flavor 4.0% nicotine
OTHERmyblu Honeymoon 2.5%
Ad-libitum use of myblu e-cigarette with Honeymoon flavor 2.5% nicotine
OTHERmyblu Honeymoon 4.0%
Ad-libitum use of myblu e-cigarette with Honeymoon flavor 4.0% nicotine
OTHERJUUL 5%
Ad-libitum use of JUUL 5% e-cigarette
Sponsors
Fontem Ventures BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Concentration of Carboxyhemoglobin in Blood | Baseline and 56 days | Change from baseline in the % saturation of carboxyhemoglobin (COHb) in whole blood |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Myblu Tobacco Flavor 2.5% Use of myblu e-cigarette system with tobacco flavor 2.5% nicotine | 42 |
| Myblu Tobacco Flavor 4.0% Use of myblu e-cigarette system with tobacco flavor 4.0% nicotine | 42 |
| Myblu Honeymoon 2.5% Use of myblu e-cigarette system with Honeymoon flavor 2.5% nicotine | 45 |
| Myblu Honeymoon 4.0% Use of myblu e-cigarette system with Honeymoon flavor 4.0% nicotine | 46 |
| Continue-smoking The subject's usual brand of combustible cigarette
Continue-smoking: Ad-libitum use of subjects' usual brand combustible cigarette | 44 |
| Total | 219 |
Baseline characteristics
| Characteristic | Myblu Tobacco Flavor 4.0% | Myblu Honeymoon 2.5% | Myblu Honeymoon 4.0% | Myblu Tobacco Flavor 2.5% | Continue-smoking | Total |
|---|---|---|---|---|---|---|
| 3-hydroxypropylmercapturic acid (3-HPMA) amount excreted in urine | 1730.3 ug/24 hours STANDARD_DEVIATION 1044.2 | 1749.7 ug/24 hours STANDARD_DEVIATION 780.1 | 1919.0 ug/24 hours STANDARD_DEVIATION 999.8 | 1592.5 ug/24 hours STANDARD_DEVIATION 818.2 | 2214.0 ug/24 hours STANDARD_DEVIATION 1172.6 | 1841.1 ug/24 hours STANDARD_DEVIATION 963 |
| 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) amount excreted in urine | 406.8 ng/24 hours STANDARD_DEVIATION 328.8 | 410.4 ng/24 hours STANDARD_DEVIATION 351.2 | 479.4 ng/24 hours STANDARD_DEVIATION 404.2 | 411.0 ng/24 hours STANDARD_DEVIATION 333.2 | 513.7 ng/24 hours STANDARD_DEVIATION 403.7 | 444.26 ng/24 hours STANDARD_DEVIATION 346.2 |
| Age, Continuous | 37.8 years STANDARD_DEVIATION 10.47 | 40.3 years STANDARD_DEVIATION 9.43 | 40.3 years STANDARD_DEVIATION 9.75 | 39.9 years STANDARD_DEVIATION 11.72 | 39.7 years STANDARD_DEVIATION 10.44 | 39.6 years STANDARD_DEVIATION 10.32 |
| Blood carboxyhemoglobin (COHb) % | 4.8 % saturation STANDARD_DEVIATION 1.8 | 4.8 % saturation STANDARD_DEVIATION 2.1 | 5.3 % saturation STANDARD_DEVIATION 1.9 | 4.9 % saturation STANDARD_DEVIATION 2.2 | 5.7 % saturation STANDARD_DEVIATION 2 | 5.1 % saturation STANDARD_DEVIATION 2 |
| Body mass index (BMI) | 30.0 kg/m^2 STANDARD_DEVIATION 4.9 | 28.9 kg/m^2 STANDARD_DEVIATION 4.7 | 28.9 kg/m^2 STANDARD_DEVIATION 5.2 | 28.0 kg/m^2 STANDARD_DEVIATION 4.7 | 29.9 kg/m^2 STANDARD_DEVIATION 5.6 | 29.1 kg/m^2 STANDARD_DEVIATION 5.1 |
| Level of white blood cells | 7.0 cells*thousands/uL STANDARD_DEVIATION 2 | 6.8 cells*thousands/uL STANDARD_DEVIATION 1.8 | 7.4 cells*thousands/uL STANDARD_DEVIATION 2 | 7.7 cells*thousands/uL STANDARD_DEVIATION 2 | 7.2 cells*thousands/uL STANDARD_DEVIATION 2.2 | 7.2 cells*thousands/uL STANDARD_DEVIATION 2 |
| Nicotine equivalents amount excreted in urine | 14.1 mg/24 hours STANDARD_DEVIATION 7.5 | 17.1 mg/24 hours STANDARD_DEVIATION 13.3 | 16.2 mg/24 hours STANDARD_DEVIATION 6.5 | 13.6 mg/24 hours STANDARD_DEVIATION 6.8 | 18.0 mg/24 hours STANDARD_DEVIATION 7.3 | 15.8 mg/24 hours STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 18 Participants | 16 Participants | 12 Participants | 13 Participants | 75 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) White | 23 Participants | 24 Participants | 27 Participants | 27 Participants | 30 Participants | 131 Participants |
| Sex: Female, Male Female | 14 Participants | 18 Participants | 20 Participants | 14 Participants | 18 Participants | 84 Participants |
| Sex: Female, Male Male | 28 Participants | 27 Participants | 26 Participants | 28 Participants | 26 Participants | 135 Participants |
| S-phenyl mercapturic acid (S-PMA) amount excreted in urine | 5.9 ug/24 hours STANDARD_DEVIATION 4.3 | 6.5 ug/24 hours STANDARD_DEVIATION 5.1 | 7.2 ug/24 hours STANDARD_DEVIATION 5.2 | 5.3 ug/24 hours STANDARD_DEVIATION 3.7 | 8.6 ug/24 hours STANDARD_DEVIATION 5.9 | 6.7 ug/24 hours STANDARD_DEVIATION 4.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 71 | 0 / 47 | 0 / 57 | 0 / 44 | 0 / 21 |
| other Total, other adverse events | 8 / 55 | 10 / 71 | 6 / 47 | 6 / 57 | 7 / 44 | 8 / 21 |
| serious Total, serious adverse events | 0 / 55 | 0 / 71 | 0 / 47 | 0 / 57 | 0 / 44 | 0 / 21 |
Outcome results
Primary
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
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | -60.0 % change from baseline | Standard Deviation 28.2 |
| Myblu Tobacco Flavor 4.0% | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | -55.7 % change from baseline | Standard Deviation 46.1 |
| Myblu Honeymoon 2.5% | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | -50.5 % change from baseline | Standard Deviation 36.2 |
| Myblu Honeymoon 4.0% | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | -53.8 % change from baseline | Standard Deviation 64.5 |
| Continue-smoking | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | 1.6 % change from baseline | Standard Deviation 40.6 |
Primary
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
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | -58.3 % change from baseline | Standard Deviation 72.8 |
| Myblu Tobacco Flavor 4.0% | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | -44.7 % change from baseline | Standard Deviation 150.5 |
| Myblu Honeymoon 2.5% | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | -62.7 % change from baseline | Standard Deviation 36.2 |
| Myblu Honeymoon 4.0% | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | -70.7 % change from baseline | Standard Deviation 33.7 |
| Continue-smoking | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | 1.1 % change from baseline | Standard Deviation 29.6 |
Primary
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
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | -85.9 % change from baseline | Standard Deviation 32.5 |
| Myblu Tobacco Flavor 4.0% | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | -44.9 % change from baseline | Standard Deviation 257.5 |
| Myblu Honeymoon 2.5% | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | -63.1 % change from baseline | Standard Deviation 79.3 |
| Myblu Honeymoon 4.0% | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | -73.8 % change from baseline | Standard Deviation 55.7 |
| Continue-smoking | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | -2.7 % change from baseline | Standard Deviation 38.4 |
Primary
Concentration of Carboxyhemoglobin in Blood
Change from baseline in the % saturation of carboxyhemoglobin (COHb) in whole blood
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Concentration of Carboxyhemoglobin in Blood | -59.6 % change from baseline | Standard Deviation 23.3 |
| Myblu Tobacco Flavor 4.0% | Concentration of Carboxyhemoglobin in Blood | -62.7 % change from baseline | Standard Deviation 19.4 |
| Myblu Honeymoon 2.5% | Concentration of Carboxyhemoglobin in Blood | -46.4 % change from baseline | Standard Deviation 35.1 |
| Myblu Honeymoon 4.0% | Concentration of Carboxyhemoglobin in Blood | -62.7 % change from baseline | Standard Deviation 21.2 |
| Continue-smoking | Concentration of Carboxyhemoglobin in Blood | 8.5 % change from baseline | Standard Deviation 28.3 |
Secondary
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
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Amount of Nicotine Equivalents in Urine in 24 Hours | -7.8 % change from baseline | Standard Deviation 74 |
| Myblu Tobacco Flavor 4.0% | Amount of Nicotine Equivalents in Urine in 24 Hours | 16.6 % change from baseline | Standard Deviation 61.1 |
| Myblu Honeymoon 2.5% | Amount of Nicotine Equivalents in Urine in 24 Hours | -13.8 % change from baseline | Standard Deviation 54.5 |
| Myblu Honeymoon 4.0% | Amount of Nicotine Equivalents in Urine in 24 Hours | -1.3 % change from baseline | Standard Deviation 38.8 |
| Continue-smoking | Amount of Nicotine Equivalents in Urine in 24 Hours | -7.0 % change from baseline | Standard Deviation 27 |
Secondary
Level of White Blood Cells
The change from baseline in the level of white blood cells, which is a biomarker of potential harm
Time frame: Baseline and 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Level of White Blood Cells | -9.2 % change from baseline | Standard Deviation 16.7 |
| Myblu Tobacco Flavor 4.0% | Level of White Blood Cells | -4.3 % change from baseline | Standard Deviation 16.8 |
| Myblu Honeymoon 2.5% | Level of White Blood Cells | -8.7 % change from baseline | Standard Deviation 17.9 |
| Myblu Honeymoon 4.0% | Level of White Blood Cells | -8.5 % change from baseline | Standard Deviation 16.3 |
| Continue-smoking | Level of White Blood Cells | 4.7 % change from baseline | Standard Deviation 17 |
Secondary
Maximum Nicotine Concentration in Blood
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
Population: Sub-group of participants who participated in the PK sub-study, on Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Maximum Nicotine Concentration in Blood | 4.0 ng/mL | Geometric Coefficient of Variation 196.3 |
| Myblu Tobacco Flavor 4.0% | Maximum Nicotine Concentration in Blood | 7.3 ng/mL | Geometric Coefficient of Variation 118.6 |
| Myblu Honeymoon 2.5% | Maximum Nicotine Concentration in Blood | 4.3 ng/mL | Geometric Coefficient of Variation 191.3 |
| Myblu Honeymoon 4.0% | Maximum Nicotine Concentration in Blood | 8.9 ng/mL | Geometric Coefficient of Variation 159.8 |
| Continue-smoking | Maximum Nicotine Concentration in Blood | 13.5 ng/mL | Geometric Coefficient of Variation 62.5 |
| JUUL® 5.0% | Maximum Nicotine Concentration in Blood | 6.9 ng/mL | Geometric Coefficient of Variation 160.1 |
Secondary
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.
Time frame: 56 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Myblu Tobacco Flavor 2.5% | Subjective Measure: Nicotine Withdrawal Symptoms Total Score | 8.6 score on a scale | Standard Deviation 6.7 |
| Myblu Tobacco Flavor 4.0% | Subjective Measure: Nicotine Withdrawal Symptoms Total Score | 5.7 score on a scale | Standard Deviation 5.5 |
| Myblu Honeymoon 2.5% | Subjective Measure: Nicotine Withdrawal Symptoms Total Score | 7.1 score on a scale | Standard Deviation 5.3 |
| Myblu Honeymoon 4.0% | Subjective Measure: Nicotine Withdrawal Symptoms Total Score | 6.8 score on a scale | Standard Deviation 5.8 |
| Continue-smoking | Subjective Measure: Nicotine Withdrawal Symptoms Total Score | 8.1 score on a scale | Standard Deviation 5.9 |