Multiple-dose Nicotine Pharmacokinetics With Three Oral Nicotine Replacement Products

Study Overview
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Brief Summary
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Multiple-dose nicotine pharmacokinetics with three oral nicotine replacement products. A study in healthy smokers.

Detailed Description
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Fifty (50) healthy male or female subjects between the ages of 19 and 50 years, inclusive, smoking at least 20 cigarettes daily during at least one year preceding inclusion. Multiple doses of all study treatments are given either every 60 minutes or every 90 minutes, respectively. All products will be administered in accordance with labeling, on five separate treatment visits. The subjects will abstain from smoking from 8 pm in the evening before and until the end of each visit.

Official Title
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Multiple-dose Nicotine Pharmacokinetics With Three Oral Nicotine Replacement Products. A Study in Healthy Smokers.

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Nicotine
* Drug: Nicotine
* Drug: Nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, smoking at least 20 cigarettes daily during at least one year preceding inclusion. BMI between 17.5 and 30.0 kg/m2 and a total body weight of at least 55.0 kg. 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. Willing and able to comply with all scheduled visits and study procedures 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. Any medical condition or history that might, per protocol or in the opinion of the investigator, compromise subject safety or trial results.

Ages Eligible for Study
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Minimum Age: 19 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NRT 60<br>A 6 mg dose of an experimental Nicotine Replacement Therapy (NRT) given every hour for 11 hours, with a 36-hour washout between visits | Drug: Nicotine<br>* 6 mg experimental Nicotine Replacement Therapy (NRT)<br>* Other names: Not yet marketed;|
| Active Comparator: NFG 60<br>A 4 mg dose of a marketed Nicotine Fruit Gum (NFG) given every hour for 11 hours, with a 36-hour washout between visits | Drug: Nicotine<br>* 4 mg marketed Nicotine Fruit Gum (NFG)<br>* Other names: Nicorette® Freshfruit Gum;|
| Experimental: NRT 90<br>A 6 mg dose of NRT given every 90 minutes for 10.5 hours, with a 36-hour washout between visits | Drug: Nicotine<br>* 6 mg experimental Nicotine Replacement Therapy (NRT)<br>* Other names: Not yet marketed;|
| Active Comparator: NFG 90<br>A 4 mg dose of NFG given every 90 minutes for 10.5 hours, with a 36-hour washout between visits | Drug: Nicotine<br>* 4 mg marketed Nicotine Fruit Gum (NFG)<br>* Other names: Nicorette® Freshfruit Gum;|
| Active Comparator: NIQ 60<br>A 4 mg dose of marketed nicotine mint lozenge (NIQ), given every hour for 11 hours, with a 36-hour washout between visits | Drug: Nicotine<br>* 4 mg marketed nicotine mint lozenge (NIQ)<br>* Other names: NiQuitinTM Mint lozenge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration | Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma within the last dosing interval, measured in nanograms/milliliter (ng/mL) | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 
| Average Concentration | Average Nicotine Plasma Concentration (Cav) within the last dosing interval | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 
| Area Under the Curve | Area under the nicotine plasma concentration-vs.-time curve during the last dosing interval (AUCt) | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Concentration | The time at which maximum concentration is reached (Tmax) | During 12 hours post-dose | 
| Minimum Observed Concentration | Minimum Observed Plasma Concentration (Cmin), which is the minimum concentration (amount of drug) measurable in blood plasma within the last dosing interval, measured in nanograms/milliliter (ng/mL) | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 
| Peak-Trough Fluctuation | Percent of Peak-Trough Fluctuation in one dosing interval at steady state (PTF) | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 
| Swing | Swing in one dosing interval at steady state, calculated as (Cmax-Cmin)/ Cmin | within the last dosing interval (starting at 10.5-11 hours after first product administration) | 
| Nicotine Released | The amount of nicotine released from the product during product administration | 30 minutes | 

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