Multiple-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product.

Study Overview
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Brief Summary
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A comparison of three products for oral nicotine replacement with respect to pharmacokinetics after multiple-doses of nicotine.

Detailed Description
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This study compares a new oral Nicotine Replacement Therapy (NRT) product with NiQuitin™ lozenge 4 mg and Nicorette®gum 4 mg, after 12 hours of nicotine abstinence, with respect to steady-state nicotine pharmacokinetics, during 12 hours after start of the first administration. Multiple doses of each treatment are given once hourly during five separate treatment visits scheduled in a crossover setting with randomized treatment sequences. The study will include 40 healthy smokers between 18-50 years, who have been smoking at least 20 cigarettes daily during at least one year preceding inclusion. Subjects and study personnel will be aware of which treatment is administered at a given visit.

Official Title
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Multiple-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product. A Study in Healthy Smokers.

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Oral Nicotine
* Drug: Nicotine Lozenge
* Drug: Nicotine gum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy smokers, smoking at least 20 cigarettes daily during at least one year preceding inclusion and BMI between 17.5 and 30.0 kg/m2. Female participants of child-bearing potential are required to use a medically acceptable means of birth control. A personally signed and dated informed consent document, indicating that the subject has been informed of all pertinent aspects of the study. Exclusion Criteria: Pregnancy, lactation or intended pregnancy. Treatment with an investigational product or donation or loss of blood within 3 month preceding the first dose of study medication. Prior regular use of nicotine mouth spray

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Nicotine 24-SA<br>2 Self-administrations of Experimental Nicotine once every hour | Drug: Oral Nicotine<br>* Oral Nicotine either self-administered or provided by study personnel within 12 hours<br>* Other names: generic Nicotine;|
| Experimental: Oral Nicotine 24<br>2 administrations of Experimental Nicotine by study personnel once every hour | Drug: Oral Nicotine<br>* Oral Nicotine either self-administered or provided by study personnel within 12 hours<br>* Other names: generic Nicotine;|
| Experimental: Oral Nicotine 48<br>2 administrations of Experimental Nicotine by study personnel once every 30 minutes | Drug: Oral Nicotine<br>* Oral Nicotine either self-administered or provided by study personnel within 12 hours<br>* Other names: generic Nicotine;|
| Active Comparator: NiQuitin™ Lozenge 4 mg<br>1 NiQuitin™ lozenge, administered by study personnel once every hour | Drug: Nicotine Lozenge<br>* Nicotine lozenge marketed as NiQuitin™ 4 mg hourly within 12 hours<br>* Other names: NiQuitin™;|
| Active Comparator: Nicorette® Gum 4 mg<br>1 piece Nicorette® gum, chewed for 30 minutes once every hour | Drug: Nicotine gum<br>* Nicotine gum marketed as Nicorette® 4 mg hourly within 12 hours<br>* Other names: Nicorette®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration | Cmax, which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered measured in nanograms/milliliter (ng/ml) | During the last dosing interval (hour 11-12 post-dose) | 
| Average Concentration | Pharmacokinetic measurement - average concentration during the last dosing interval (AUCtau) | During the last dosing interval (hour 11-12 post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Concentration | The time at which maximum concentration is reached (Tmax) | During the last dosing interval (hour 11-12 post-dose) | 
| Minimum Plasma Concentration | The minimum nicotine plasma concentration during the last dosing interval (Cmin) | During the last dosing interval (hour 11-12 post-dose) | 
| Peak-Trough Fluctuation | Percent of peak-trough fluctuation over one dosing interval at steady state (PTF) | During the last dosing interval (hour 11-12 post-dose) | 
| Nicotine Plasma Concentration | The nicotine concentration in plasma (area under the nicotine plasma concentration curve) 1 hour after start of treatment | One hour after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking Cessation, Nicotine pharmacokinetics