A Bioavailability Study of Nicotine Delivered by an Electronic Vapour Product

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised, Crossover, Relative Bioavailability Study of Nicotine Delivered by an Electronic Vapour Product, a Nicotine Inhalator and a Conventional Cigarette

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: EVP unflavoured
* Other: EVP flavoured
* Other: Nicotine inhalator
* Other: Conventional cigarette


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Subjects use the unflavoured EVP on Day 1, the flavoured EVP on Day 2, the nicotine inhalator on Day 3 and the conventional cigarette on Day 4. | Other: EVP unflavoured<br> <br> Other: EVP flavoured<br> <br> Other: Nicotine inhalator<br>* 15 mg nicotine Nicorette<br>Other: Conventional cigarette<br> <br> |
| Experimental: Sequence 2<br>Subjects use 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. | Other: EVP unflavoured<br> <br> Other: EVP flavoured<br> <br> Other: Nicotine inhalator<br>* 15 mg nicotine Nicorette<br>Other: Conventional cigarette<br> <br> |
| Experimental: Sequence 3<br>Subjects use the nicotine inhalator on Day 1, the conventional cigarette on Day 2, the unflavoured EVP on Day 3 and the flavoured EVP on Day 4. | Other: EVP unflavoured<br> <br> Other: EVP flavoured<br> <br> Other: Nicotine inhalator<br>* 15 mg nicotine Nicorette<br>Other: Conventional cigarette<br> <br> |
| Experimental: Sequence 4<br>Subjects use the conventional cigarette on Day 1, the nicotine inhalator on Day 2, the flavoured EVP on Day 3 and the unflavoured EVP on Day 4. | Other: EVP unflavoured<br> <br> Other: EVP flavoured<br> <br> Other: Nicotine inhalator<br>* 15 mg nicotine Nicorette<br>Other: Conventional cigarette<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Plasma Concentration | Maximum plasma nicotine concentration (Cmax) | 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, 15, 30, 45, 60 minutes, 2, 4, 6, 8, 12 and 21 hours | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exhaled Carbon Monoxide | Measured with a Smokerlyser device | 25 minutes | 
| 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. | 30 minutes after the third product use | 
| 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. | 30 minutes after the third product use |