4 mg Nicotine Polacrilex Gum and Swedish Portion Snus

Study Overview
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Brief Summary
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Fifteen healthy smokers are given single doses of General Onyx 1 g portion snus and General White 1g portion snus, respectively, and one piece of Nicorette 4 mg chewing gum. Serial blood samples are drawn before (0), 2, 4, 8, 16, 24, 30, 45, 60 minutes, 1.5, 2, 4, 6 and 8 hours after administration for determination of nicotine. Mean + SD extracted dose of nicotine from each preparation will be estimated. The percentage extracted of the nicotine content will be calculated. Cmax and Tmax will be estimated. A comparison to Nicorette 4 mg chewing gum will be made. The dose absorbed into the systemic blood circulation (AUC) in relation to the dose following the 4 mg Nicorette chewing gum will be calculated. Self-reports of subjective effects will be obtained up to 30 minutes after the test product is administered using a 100 mm visual analogue scale (VAS) anchored with not at all to extremely. Study hypothesis is that Cmax and AUC of Nicorette 4 mg chewing gum and Swedish snus are similar.

Detailed Description
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Fifteen healthy smokers are given single doses of General Onyx 1 g portion snus and General White 1g portion snus, respectively, and one piece of Nicorette 4 mg chewing gum. Serial blood samples are drawn before (0), 2, 4, 8, 16, 24, 30, 45, 60 minutes, 1.5, 2, 4, 6 and 8 hours after administration for determination of nicotine. Mean + SD extracted dose of nicotine from each preparation will be estimated. The percentage extracted of the nicotine content will be calculated. Cmax and Tmax will be estimated. A comparison to Nicorette 4 mg chewing gum will be made. The dose absorbed into the systemic blood circulation (AUC) in relation to the dose following the 4 mg Nicorette chewing gum will be calculated. Self-reports of subjective effects will be obtained up to 30 minutes after the test product is administered using a 100 mm visual analogue scale (VAS) anchored with not at all to extremely. The subjects are male and female smokers, smoking a minimum of 7 cigarettes per day. They should have no history of cardiac, kidney or hepatic disease, alcohol abuse or drug dependence. A physical examination including ECG and blood pressure should give no evidence of disease. No abnormalities should be found in a routine laboratory screening. The subjects are requested not to smoke or to use any other form of nicotine containing products from 8 p.m. the day before each session until the last blood sample in each session. Previous experience has shown that subjects that have abstained from smoking for 12 hours have a plasma nicotine value of <4 ng/ml. A value >4 ng/ml prior to start of administration should lead to exclusion from statistical analysis. The subjects must be fasting overnight from 12 p.m. the day before each session. No food and drink are allowed from 15 minutes prior to and until 60 minutes after drug administration.

Official Title
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Nicotine Delivery and Subjective Effects of 4 mg Nicotine Polacrilex Chewing Gum Compared With Swedish Portion Snus

Conditions
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Healthy Subjects, Smokers

Intervention / Treatment
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* Drug: Nicotine
* Drug: Nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer, smoking >7 cigarettes per day. No use of smokeless tobacco and nicotine containing products is allowed. Fasting overnight. Exclusion Criteria: Use of smokeless tobacco and nicotine containing products is not allowed from 8 p.m. the day before trial day. Subjects tested with Smokelyzer for exhaled carbon monoxide.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Swedish Snus Type 1<br>The subject keeps one pouch of snus still between the upper lip and the gum for 30 minutes. Amount of nicotine extracted, plasma nicotine concentration at 30 minutes (C30), Tmax, Cmax, AUCinf and heart rate for each treatment. | Drug: Nicotine<br>* Nicotine pouch, 2.2 mg, single dose, 30 minutes<br>* Other names: General White 1g portion snus;|
| Active Comparator: Swedish Snus Type 2<br>The subject keeps one pouch of snus still between the upper lip and the gum for 30 minutes. Amount of nicotine extracted, plasma nicotine concentration at 30 minutes (C30), Tmax, Cmax, AUCinf and heart rate for each treatment. | Drug: Nicotine<br>* Nicotine pouch, 2.2 mg, single dose, 30 minutes<br>* Other names: General White 1g portion snus;|
| Active Comparator: 4 mg Nicorette chewing gum<br>Nicorette is chewed according to instructions in package insert over 30 minutes. | Drug: Nicotine<br>* Chewing Gum, 4 mg, single dose, 30 minutes<br>* Other names: Nicorette 4 mg chewing gum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic/Dynamic Equvivalence | After baseline measurements, plasma nicotine concentrations are monitored over 8 hours. Each subject's rating of subjective symptoms, e.g. product strength using a 100 mm visual analogue scale (VAS) anchored with not at all to extremely is recorded up to 30 minutes after dosing. | 8 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine Polacrilex chewing gum versus Swedish Snus