Healthy Volunteers
Conditions
Brief summary
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.
Interventions
OTHERMyblu variant A
Use of Myblu e-cigarette with flavor A 2.4% nicotine
OTHERMyblu variant B
Use of Myblu e-cigarette with flavor B 3.6% nicotine
OTHERMyblu variant C
Use of Myblu e-cigarette with flavor C 2.5% nicotine
OTHERMyblu variant D
Use of Myblu e-cigarette with flavor D 4.0% nicotine
OTHERMyblu variant E
Use of Myblu e-cigarette with flavor E 3.6% nicotine
OTHERMyblu variant F
Use of Myblu e-cigarette with flavor F 2.4% nicotine
OTHERMyblu variant G
Use of Myblu e-cigarette with flavor G 4.0% nicotine
OTHERMyblu variant H
Use of Myblu e-cigarette with flavor H 3.6% nicotine
Sponsors
Fontem Ventures BV
Fontem US LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | Baseline and 8 days | 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). |
| Maximum Nicotine Concentration in Blood | 180 minutes following the start of the controlled product use session on Day 2 (12 measurements over the period) | Maximum nicotine concentration in blood (Cmax) |
| Concentration of Carboxyhemoglobin in Blood | Baseline and 8 days | Change from baseline in the concentration of carboxyhemoglobin (COHb) in whole blood. |
| Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | Baseline and 8 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 (NNK), excreted in urine during 24 hours (creatinine adjusted). |
| Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | Baseline and 8 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spirometry: Forced Expiratory Volume in 1 Second | Baseline and 8 days | 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. |
| Spirometry: Forced Vital Capacity | Baseline and 8 days | 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. |
| Subjective Measure: Urge to Smoke | 8 days | Urge to smoke score: Subjects answer the following question How strong is your urge to smoke right now? using a visual analogue scale (VAS). 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. |
| Level of White Blood Cells | Baseline and 8 days | The change from baseline in the level of white blood cells, a biomarker of potential harm. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABDC Subjects use MybluTM e-cigarette product variant A (2.4 % nicotine) ad libitum for 2 days, then switch to use variant B (3.6% nicotine) for 2 days, then D (4.0% nicotine) for 2 days and then C (2.5% nicotine) for 2 days. A 12-hour washout period 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). | 5 |
| BCAD Same as previous but in a different randomization order | 5 |
| CDBA Same as previous but in a different randomization order | 5 |
| DACB Same as previous but in a different randomization order | 5 |
| EFHG Subjects use MybluTM e-cigarette product variant E (3.6 % nicotine) ad libitum for 2 days, then switch to use variant F (2.4% nicotine) for 2 days, then H (3.6% nicotine) for 2 days and then G (4.0% nicotine) for 2 days. A 12-hour washout period 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). | 5 |
| FGEH Same as previous but in a different randomization order | 5 |
| GHFE Same as previous but in a different randomization order | 5 |
| HEGF Same as previous but in a different randomization order | 5 |
| Total | 40 |
Baseline characteristics
| Characteristic | ABDC | BCAD | CDBA | DACB | EFHG | FGEH | GHFE | HEGF | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 15.28 | 38.6 years STANDARD_DEVIATION 14.03 | 47.6 years STANDARD_DEVIATION 8.73 | 37.8 years STANDARD_DEVIATION 10.76 | 44.6 years STANDARD_DEVIATION 10.88 | 41.6 years STANDARD_DEVIATION 11.19 | 43.0 years STANDARD_DEVIATION 11.51 | 47.2 years STANDARD_DEVIATION 12.58 | 43.3 years STANDARD_DEVIATION 11.45 |
| BMI | 25.8 kg/m^2 STANDARD_DEVIATION 4.5 | 29.3 kg/m^2 STANDARD_DEVIATION 2.1 | 29.4 kg/m^2 STANDARD_DEVIATION 5.5 | 29.2 kg/m^2 STANDARD_DEVIATION 4.3 | 26.4 kg/m^2 STANDARD_DEVIATION 7.3 | 25.3 kg/m^2 STANDARD_DEVIATION 3.3 | 28.2 kg/m^2 STANDARD_DEVIATION 3.7 | 27.5 kg/m^2 STANDARD_DEVIATION 3.3 | 27.6 kg/m^2 STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 1 Participants | 24 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 1 / 19 | 4 / 19 | 3 / 19 | 2 / 20 | 3 / 19 | 2 / 19 | 0 / 20 | 3 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 20 |
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 during 24 hours (creatinine adjusted).
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | Baseline value | 1242.2 ug/g creatinine | Standard Deviation 536 |
| Product Variant A | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | Change from baseline | -1097.1 ug/g creatinine | Standard Deviation 522.2 |
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 (NNK), excreted in urine during 24 hours (creatinine adjusted).
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | Baseline value | 345.4 ng/g creatinine | Standard Deviation 252.3 |
| Product Variant A | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | Change from baseline | -262.8 ng/g creatinine | Standard Deviation 205.1 |
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 during 24 hours (creatinine adjusted).
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | Baseline value | 5.9 ug/g creatinine | Standard Deviation 4.2 |
| Product Variant A | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | Change from baseline | -5.9 ug/g creatinine | Standard Deviation 4.1 |
Primary
Concentration of Carboxyhemoglobin in Blood
Change from baseline in the concentration of carboxyhemoglobin (COHb) in whole blood.
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Concentration of Carboxyhemoglobin in Blood | Baseline value | 7.7 % saturation | Standard Deviation 2.1 |
| Product Variant A | Concentration of Carboxyhemoglobin in Blood | Change from baseline | -6.25 % saturation | Standard Deviation 2.06 |
Primary
Maximum Nicotine Concentration in Blood
Maximum nicotine concentration in blood (Cmax)
Time frame: 180 minutes following the start of the controlled product use session on Day 2 (12 measurements over the period)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Product Variant A | Maximum Nicotine Concentration in Blood | 3.6 ng/mL | Geometric Coefficient of Variation 91.6 |
| Product Variant B | Maximum Nicotine Concentration in Blood | 5.3 ng/mL | Geometric Coefficient of Variation 109.6 |
| Product Variant C | Maximum Nicotine Concentration in Blood | 4.0 ng/mL | Geometric Coefficient of Variation 113.5 |
| Product Variant D | Maximum Nicotine Concentration in Blood | 5.3 ng/mL | Geometric Coefficient of Variation 106.4 |
| Product Variant E | Maximum Nicotine Concentration in Blood | 6.5 ng/mL | Geometric Coefficient of Variation 135.7 |
| Product Variant F | Maximum Nicotine Concentration in Blood | 4.6 ng/mL | Geometric Coefficient of Variation 143.4 |
| Product Variant G | Maximum Nicotine Concentration in Blood | 8.0 ng/mL | Geometric Coefficient of Variation 99.6 |
| Product Variant H | Maximum Nicotine Concentration in Blood | 9.3 ng/mL | Geometric Coefficient of Variation 95.8 |
Secondary
Level of White Blood Cells
The change from baseline in the level of white blood cells, a biomarker of potential harm.
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Level of White Blood Cells | Baseline value | 7.5 cells*10^9/L | Standard Deviation 1.7 |
| Product Variant A | Level of White Blood Cells | Change from baseline | -0.4 cells*10^9/L | Standard Deviation 1.1 |
Secondary
Spirometry: Forced Expiratory Volume in 1 Second
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.
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Spirometry: Forced Expiratory Volume in 1 Second | Baseline value | 2.9 L | Standard Deviation 1.2 |
| Product Variant A | Spirometry: Forced Expiratory Volume in 1 Second | 8 days timepoint | 3.2 L | Standard Deviation 0.9 |
Secondary
Spirometry: Forced Vital Capacity
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.
Time frame: Baseline and 8 days
Population: The arms are combined into one group, because the aim was to compare biomarkers in all participants who use any e-cigarette variant, to the value at baseline (when they were smoking conventional cigarettes). Data is missing for 2 participants at the 8 days timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Spirometry: Forced Vital Capacity | Baseline value | 3.8 L | Standard Deviation 1.5 |
| Product Variant A | Spirometry: Forced Vital Capacity | 8 days timepoint | 4.2 L | Standard Deviation 1.2 |
Secondary
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 (VAS). 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.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product Variant A | Subjective Measure: Urge to Smoke | 70.4 score on a scale | Standard Deviation 18.7 |
| Product Variant B | Subjective Measure: Urge to Smoke | 67.8 score on a scale | Standard Deviation 24.8 |
| Product Variant C | Subjective Measure: Urge to Smoke | 67.2 score on a scale | Standard Deviation 21.7 |
| Product Variant D | Subjective Measure: Urge to Smoke | 63.7 score on a scale | Standard Deviation 22.1 |
| Product Variant E | Subjective Measure: Urge to Smoke | 62.0 score on a scale | Standard Deviation 31.6 |
| Product Variant F | Subjective Measure: Urge to Smoke | 56.2 score on a scale | Standard Deviation 34.4 |
| Product Variant G | Subjective Measure: Urge to Smoke | 62.9 score on a scale | Standard Deviation 32.1 |
| Product Variant H | Subjective Measure: Urge to Smoke | 63.0 score on a scale | Standard Deviation 29.4 |