4 mg Nicotine Polacrilex Gum and Swedish Portion Snus (SMWS06)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Smokers
• Intervention / Treatment: Drug: Nicotine; Drug: Nicotine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Skane
    • Eslov, Skane, Sweden, 241 23
      • Carema AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Swedish Snus Type 1; 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; Nicotine pouch, 2.2 mg, single dose, 30 minutes; Other Names: General Onyx 1 g portion snus; General White 1g portion snus; Drug: Nicotine; Chewing Gum, 4 mg, single dose, 30 minutes; Other Names: Nicorette 4 mg chewing gum
Active Comparator: Swedish Snus Type 2; 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; Nicotine pouch, 2.2 mg, single dose, 30 minutes; Other Names: General Onyx 1 g portion snus; General White 1g portion snus; Drug: Nicotine; Chewing Gum, 4 mg, single dose, 30 minutes; Other Names: Nicorette 4 mg chewing gum
Active Comparator: 4 mg Nicorette chewing gum; Nicorette is chewed according to instructions in package insert over 30 minutes.	Drug: Nicotine; Nicotine pouch, 2.2 mg, single dose, 30 minutes; Other Names: General Onyx 1 g portion snus; General White 1g portion snus; Drug: Nicotine; Chewing Gum, 4 mg, single dose, 30 minutes; Other Names: Nicorette 4 mg chewing gum

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Contract Research Organization el AB
• Collaborators: Swedish Match AB

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 11, 2010
• First Posted (Estimate): August 16, 2010

Study Record Updates

• Last Update Posted (Estimate): August 16, 2010
• Last Update Submitted That Met QC Criteria: August 11, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Nicotine Polacrilex chewing gum versus Swedish Snus
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: SMWS06