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 flavor A_2.4
Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine
OTHERMyblu flavor B_2.4
Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine
OTHERMyblu flavor C_2.4
Use of Myblu e-cigarette with flavor C at 2.4% nicotine
OTHERMyblu flavor D_2.4
Use of Myblu e-cigarette with flavor D at 2.4% nicotine
OTHERMyblu flavor E_1.2
Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine
OTHERMyblu flavor F_1.2
Fse of Myblu e-cigarette with flavor F at 1.2% nicotine
OTHERMyblu flavor G_2.4
Use of Myblu e-cigarette with flavor G at 2.4% nicotine
OTHERMyblu flavor H_2.4
Use of Myblu e-cigarette with flavor H at 2.4% 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 | 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. |
| Spirometry: Forced Vital Capacity | Baseline and 8 days | 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. |
| 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. 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 |
|---|---|
| Product Use Sequence ABDC 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 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).
Myblu flavor A\_2.4: Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine
Myblu flavor B\_2.4: Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine
Myblu flavor C\_2.4: Use of Myblu e-cigarette with flavor C at 2.4% nicotine
Myblu flavor D\_2.4: Use of Myblu e-cigarette with flavor D at 2.4% nicotine | 4 |
| Product Use Sequence BCAD Same as previous arm, but in a different randomization order.
Myblu flavor A\_2.4: Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine
Myblu flavor B\_2.4: Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine
Myblu flavor C\_2.4: Use of Myblu e-cigarette with flavor C at 2.4% nicotine
Myblu flavor D\_2.4: Use of Myblu e-cigarette with flavor D at 2.4% nicotine | 5 |
| Product Use Sequence CDBA Same as previous arm, but in a different randomization order.
Myblu flavor A\_2.4: Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine
Myblu flavor C\_2.4: Use of Myblu e-cigarette with flavor C at 2.4% nicotine
Myblu flavor D\_2.4: Use of Myblu e-cigarette with flavor D at 2.4% nicotine | 5 |
| Product Use Sequence DACB Same as previous arm, but in a different randomization order.
Myblu flavor A\_2.4: Use of Myblu e-cigarette with flavor 1 at 2.4% nicotine
Myblu flavor B\_2.4: Use of Myblu e-cigarette with flavor 2 at 2.4% nicotine
Myblu flavor C\_2.4: Use of Myblu e-cigarette with flavor C at 2.4% nicotine
Myblu flavor D\_2.4: Use of Myblu e-cigarette with flavor D at 2.4% nicotine | 5 |
| Product Use Sequence EFHG 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 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).
Myblu flavor E\_1.2: Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine
Myblu flavor F\_1.2: Fse of Myblu e-cigarette with flavor F at 1.2% nicotine
Myblu flavor G\_2.4: Use of Myblu e-cigarette with flavor G at 2.4% nicotine
Myblu flavor H\_2.4: Use of Myblu e-cigarette with flavor H at 2.4% nicotine | 5 |
| Product Use Sequence FGEH Same as previous arm, but in a different randomization order.
Myblu flavor E\_1.2: Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine
Myblu flavor F\_1.2: Fse of Myblu e-cigarette with flavor F at 1.2% nicotine
Myblu flavor G\_2.4: Use of Myblu e-cigarette with flavor G at 2.4% nicotine
Myblu flavor H\_2.4: Use of Myblu e-cigarette with flavor H at 2.4% nicotine | 5 |
| Product Use Sequence GHFE Same as previous arm, but in a different randomization order.
Myblu flavor E\_1.2: Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine
Myblu flavor F\_1.2: Fse of Myblu e-cigarette with flavor F at 1.2% nicotine
Myblu flavor G\_2.4: Use of Myblu e-cigarette with flavor G at 2.4% nicotine
Myblu flavor H\_2.4: Use of Myblu e-cigarette with flavor H at 2.4% nicotine | 5 |
| Product Use Sequence HEGF Same as previous arm, but in a different randomization order.
Myblu flavor E\_1.2: Use of Myblu e-cigarette with flavor 1 at 1.2% nicotine
Myblu flavor F\_1.2: Fse of Myblu e-cigarette with flavor F at 1.2% nicotine
Myblu flavor G\_2.4: Use of Myblu e-cigarette with flavor G at 2.4% nicotine
Myblu flavor H\_2.4: Use of Myblu e-cigarette with flavor H at 2.4% nicotine | 5 |
| Total | 39 |
Baseline characteristics
| Characteristic | Product Use Sequence ABDC | Product Use Sequence BCAD | Product Use Sequence CDBA | Product Use Sequence DACB | Product Use Sequence EFHG | Product Use Sequence FGEH | Product Use Sequence GHFE | Total | Product Use Sequence HEGF |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 15.8 | 49.0 years STANDARD_DEVIATION 4.9 | 38.0 years STANDARD_DEVIATION 9.2 | 32.6 years STANDARD_DEVIATION 7.2 | 36.4 years STANDARD_DEVIATION 7 | 40.8 years STANDARD_DEVIATION 8.7 | 46.4 years STANDARD_DEVIATION 10 | 41.8 years STANDARD_DEVIATION 10 | 50.0 years STANDARD_DEVIATION 6.4 |
| Body mass index (BMI) | 25.8 kg/m^2 STANDARD_DEVIATION 4.2 | 30.5 kg/m^2 STANDARD_DEVIATION 5.5 | 28.2 kg/m^2 STANDARD_DEVIATION 5 | 26.1 kg/m^2 STANDARD_DEVIATION 4.1 | 29.4 kg/m^2 STANDARD_DEVIATION 4.4 | 29.7 kg/m^2 STANDARD_DEVIATION 7.7 | 28.5 kg/m^2 STANDARD_DEVIATION 4.2 | 28.4 kg/m^2 STANDARD_DEVIATION 5.1 | 28.7 kg/m^2 STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 9 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 5 Participants | 4 Participants | 30 Participants | 5 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 | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 14 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 25 Participants | 2 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 / 18 | 0 / 16 | 0 / 16 | 0 / 18 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 3 / 18 | 1 / 16 | 1 / 16 | 1 / 18 | 2 / 20 | 1 / 20 | 0 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 18 | 0 / 16 | 0 / 16 | 0 / 18 | 0 / 20 | 0 / 20 | 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: Data is missing for 3 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 | 756.2 ug/g creatinine | Standard Deviation 279.3 |
| Product Variant A | Amount of 3-hydroxypropylmercapturic Acid in Urine in 24 Hours | Change from baseline | -599.3 ug/g creatinine | Standard Deviation 276.6 |
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 (NNK), excreted in urine during 24 hours (creatinine adjusted).
Time frame: Baseline and 8 days
Population: Data is missing for 3 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 | 176.2 ng/g creatinine | Standard Deviation 87.4 |
| Product Variant A | Amount of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Urine in 24 Hours | Change from baseline | -134.8 ng/g creatinine | Standard Deviation 66.5 |
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: Data is missing for 3 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 | 2.6 ug/g creatinine | Standard Deviation 1.4 |
| Product Variant A | Amount of S-phenyl Mercapturic Acid in Urine in 24 Hours | Change from baseline | -2.5 ug/g creatinine | Standard Deviation 1.4 |
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: Data is missing for 3 participants at the 8 days timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Concentration of Carboxyhemoglobin in Blood | Baseline value | 5.4 % saturation | Standard Deviation 1.8 |
| Product Variant A | Concentration of Carboxyhemoglobin in Blood | Change from baseline | -4.0 % saturation | Standard Deviation 1.8 |
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 | 6.6 ng/mL | Geometric Coefficient of Variation 137.5 |
| Product Variant B | Maximum Nicotine Concentration in Blood | 7.9 ng/mL | Geometric Coefficient of Variation 91.8 |
| Product Variant C | Maximum Nicotine Concentration in Blood | 5.6 ng/mL | Geometric Coefficient of Variation 107.2 |
| Product Variant D | Maximum Nicotine Concentration in Blood | 6.0 ng/mL | Geometric Coefficient of Variation 184.5 |
| Product Variant E | Maximum Nicotine Concentration in Blood | 2.6 ng/mL | Geometric Coefficient of Variation 88.7 |
| Product Variant F | Maximum Nicotine Concentration in Blood | 2.7 ng/mL | Geometric Coefficient of Variation 91.4 |
| Product Variant G | Maximum Nicotine Concentration in Blood | 4.4 ng/mL | Geometric Coefficient of Variation 94.4 |
| Product Variant H | Maximum Nicotine Concentration in Blood | 3.5 ng/mL | Geometric Coefficient of Variation 295.6 |
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: Data is missing for 3 participants at the 8 days timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Level of White Blood Cells | Baseline value | 6.9 cells*10^9/L | Standard Deviation 1.5 |
| Product Variant A | Level of White Blood Cells | Change from baseline | -0.6 cells*10^9/L | Standard Deviation 1 |
Secondary
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.
Time frame: Baseline and 8 days
Population: Data is missing for 3 participants at the 8 days timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Spirometry: Forced Expiratory Volume in 1 Second | Baseline value | 98.0 Percent-predicted FEV1 | Standard Deviation 14.6 |
| Product Variant A | Spirometry: Forced Expiratory Volume in 1 Second | 8 days timepoint | 98.6 Percent-predicted FEV1 | Standard Deviation 16.2 |
Secondary
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.
Time frame: Baseline and 8 days
Population: Data is missing for 3 participants at the 8 days timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Product Variant A | Spirometry: Forced Vital Capacity | Baseline value | 101.0 Percent-predicted FVC | Standard Deviation 14.6 |
| Product Variant A | Spirometry: Forced Vital Capacity | 8 days timepoint | 100.3 Percent-predicted FVC | Standard Deviation 16 |
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. 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 | 72.3 score on a scale | Standard Deviation 21.9 |
| Product Variant B | Subjective Measure: Urge to Smoke | 76.4 score on a scale | Standard Deviation 13.8 |
| Product Variant C | Subjective Measure: Urge to Smoke | 64.9 score on a scale | Standard Deviation 23.4 |
| Product Variant D | Subjective Measure: Urge to Smoke | 67.6 score on a scale | Standard Deviation 26 |
| Product Variant E | Subjective Measure: Urge to Smoke | 53.7 score on a scale | Standard Deviation 32.6 |
| Product Variant F | Subjective Measure: Urge to Smoke | 54.4 score on a scale | Standard Deviation 29.5 |
| Product Variant G | Subjective Measure: Urge to Smoke | 55.4 score on a scale | Standard Deviation 29.9 |
| Product Variant H | Subjective Measure: Urge to Smoke | 59.0 score on a scale | Standard Deviation 31.5 |