Healthy Volunteers
Conditions
Brief summary
Electronic Vapour Products (EVPs) are a relatively new class of consumer products that are otherwise known as electronic cigarettes. These may look like conventional cigarettes but do not contain tobacco. The 'vapour' produced by such devices typically consists of humectants (propylene glycol or glycerol), nicotine, water, and flavours. This trial is to evaluate the pharmacokinetic profile of an EVP.
Detailed description
The principal part of this study evaluates the nicotine pharmacokinetic profile of conventional cigarettes, a nicotine inhalator, an unflavoured EVP and a flavoured EVP. A second part investigates the nicotine delivery of an EVP with four different nicotine doses.
Interventions
OTHEREVP unflavoured
OTHEREVP flavoured
OTHERNicotine inhalator
15 mg nicotine Nicorette
Sponsors
Imperial Brands PLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI of 18-35kg/m2 * Subjects must be established smokers * Subjects must have smoked five to 30 cigarettes per day for at least one year
Exclusion criteria
* Subjects who have used nicotine replacement therapy within 14 days of the screening * Subjects who have donated blood within 12 months preceding study * Subjects with relevant illness history * Subjects positive for hepatitis or HIV * Subjects with history of drug or alcohol abuse * Subjects with lung function test or vital signs considered unsuitable * Subjects who are trying to stop smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Plasma Concentration | 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, 15, 30, 45, 60 minutes, 2, 4, 6, 8, 12 and 21 hours | Maximum plasma nicotine concentration (Cmax) |
| Area Under the Concentration-time Curve for Plasma Nicotine (AUCt) | 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, 15, 30, 45, 60 minutes, 2, 4, 6, 8, 12 and 21 hours | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Carbon Monoxide | 25 minutes | Measured with a Smokerlyser device |
| Nicotine Withdrawal Symptoms | 30 minutes after the third product use | Withdrawal symptoms were evaluated with the Minnesota Nicotine Withdrawal Scale questionnaire, to which only the 15 questions of the subject's part were completed. Subjects had to rate behaviours (e.g. angry, irritable, frustrated, depressed, restless, insomnia) from 0 (none) to 4 (severe). A higher score means more severe withdrawal symptoms. Scores range from a minimum of 0 to a maximum of 60. |
| Nicotine Craving | 30 minutes after the third product use | Craving was assessed with the Brief Questionnaire of Smoking Urges (QSU-Brief). Subject had to rate 10 statements, such as I have a desire for a cigarette right now, by a number ranging from 1 (strongly disagree) to 7 (strongly agree). Scores can range from a minimum of 0 to a maximum of 70. A higher score means a stronger urge to smoke a cigarette. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Subjects in this arm used the unflavoured EVP on Day 1, the flavoured EVP on Day 2, Nicotine inhalator on Day 3 and the conventional cigarette on Day 4. | 3 |
| Sequence 2 Subjects in this arm used the flavoured EVP on Day 1, the unflavoured EVP on Day 2, the conventional cigarette on Day 3 and the Nicotine inhalator on Day 4. | 3 |
| Sequence 3 Subjects in this arm used the Nicotine inhalator on Day 1 and the conventional cigarette on Day 2, the unflavoured EVP on Day 3 and the flavoured EVP on Day 4. | 3 |
| Sequence 4 Subjects in this arm used the conventional cigarette on Day 1, the Nicotine inhalator on Day 2, the flavoured EVP on Day 3, the unflavoured EVP on Day 4. | 3 |
| Total | 12 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Region of Enrollment United Kingdom | 3 participants | 3 participants | 3 participants | 3 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 3 / 12 | 3 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Concentration-time Curve for Plasma Nicotine (AUCt)
Time frame: 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, 15, 30, 45, 60 minutes, 2, 4, 6, 8, 12 and 21 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| EVP Unflavoured | Area Under the Concentration-time Curve for Plasma Nicotine (AUCt) | 425.3 min*ng/ml | Geometric Coefficient of Variation 31.4 |
| EVP Flavoured | Area Under the Concentration-time Curve for Plasma Nicotine (AUCt) | 277.2 min*ng/ml | Geometric Coefficient of Variation 33.7 |
| Nicotine Inhalator | Area Under the Concentration-time Curve for Plasma Nicotine (AUCt) | 320.6 min*ng/ml | Geometric Coefficient of Variation 47.6 |
| Conventional Cigarette | Area Under the Concentration-time Curve for Plasma Nicotine (AUCt) | 2247.0 min*ng/ml | Geometric Coefficient of Variation 28.6 |
Primary
Nicotine Plasma Concentration
Maximum plasma nicotine concentration (Cmax)
Time frame: 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, 15, 30, 45, 60 minutes, 2, 4, 6, 8, 12 and 21 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| EVP Unflavoured | Nicotine Plasma Concentration | 3.6 ng/ml | Geometric Coefficient of Variation 33.9 |
| EVP Flavoured | Nicotine Plasma Concentration | 2.5 ng/ml | Geometric Coefficient of Variation 41.6 |
| Nicotine Inhalator | Nicotine Plasma Concentration | 2.5 ng/ml | Geometric Coefficient of Variation 45.2 |
| Conventional Cigarette | Nicotine Plasma Concentration | 21.2 ng/ml | Geometric Coefficient of Variation 43.1 |
Secondary
Exhaled Carbon Monoxide
Measured with a Smokerlyser device
Time frame: 25 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVP Unflavoured | Exhaled Carbon Monoxide | 2.5 ppm | Standard Deviation 1 |
| EVP Flavoured | Exhaled Carbon Monoxide | 2.2 ppm | Standard Deviation 0.72 |
| Nicotine Inhalator | Exhaled Carbon Monoxide | 2.3 ppm | Standard Deviation 0.78 |
| Conventional Cigarette | Exhaled Carbon Monoxide | 14.8 ppm | Standard Deviation 3.86 |
Secondary
Nicotine Craving
Craving was assessed with the Brief Questionnaire of Smoking Urges (QSU-Brief). Subject had to rate 10 statements, such as I have a desire for a cigarette right now, by a number ranging from 1 (strongly disagree) to 7 (strongly agree). Scores can range from a minimum of 0 to a maximum of 70. A higher score means a stronger urge to smoke a cigarette.
Time frame: 30 minutes after the third product use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVP Unflavoured | Nicotine Craving | 24.8 score on a scale | Standard Deviation 11.5 |
| EVP Flavoured | Nicotine Craving | 25.0 score on a scale | Standard Deviation 12.9 |
| Nicotine Inhalator | Nicotine Craving | 25.6 score on a scale | Standard Deviation 12 |
| Conventional Cigarette | Nicotine Craving | 22.8 score on a scale | Standard Deviation 14.2 |
Secondary
Nicotine Withdrawal Symptoms
Withdrawal symptoms were evaluated with the Minnesota Nicotine Withdrawal Scale questionnaire, to which only the 15 questions of the subject's part were completed. Subjects had to rate behaviours (e.g. angry, irritable, frustrated, depressed, restless, insomnia) from 0 (none) to 4 (severe). A higher score means more severe withdrawal symptoms. Scores range from a minimum of 0 to a maximum of 60.
Time frame: 30 minutes after the third product use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EVP Unflavoured | Nicotine Withdrawal Symptoms | 6.40 score on a scale | Standard Deviation 6.52 |
| EVP Flavoured | Nicotine Withdrawal Symptoms | 6.80 score on a scale | Standard Deviation 7.32 |
| Nicotine Inhalator | Nicotine Withdrawal Symptoms | 7.50 score on a scale | Standard Deviation 7.08 |
| Conventional Cigarette | Nicotine Withdrawal Symptoms | 8.10 score on a scale | Standard Deviation 8.93 |