Single-dose Pharmacokinetics of Oral Nicotine Replacement Products

Study Overview
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Brief Summary
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This is an explorative study comparing new prototypes of Nicotine Replacement Products with Nicorette® gum.

Detailed Description
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This study included 40 subjects who were randomly assigned to one of eight treatment sequences. In four of the sequences, the three prototypes with the shorter dissolution time and the reference were used; in the remaining four sequences, the three prototypes with the longer dissolution time and the reference were used. Hence, half of the subjects received the Short prototypes and half received the Long prototypes. Subjects in both treatment groups (short and long) attended four treatment visits, each of 11 hours' duration, and periods of at least 36 hours' duration between treatment visits.

Official Title
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Single-dose Pharmacokinetics of Oral Nicotine Replacement Products - An Exploratory Study in Healthy Volunteers

Conditions
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Tobacco Dependence

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy smokers, smoking at least 10 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.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 Short, no buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Experimental: A2 Short, low buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Experimental: A3 Short, high buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Experimental: B1 Long, no buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Experimental: B2 Long, low buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Experimental: B3 Long, high buffer<br>Nicotine / not yet marketed | Drug: Nicotine<br>* Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day<br>* Other names: Not yet marketed;|
| Active Comparator: R = Nicotine Gum<br>Nicorette® Gum | Drug: Nicotine Gum<br>* Following a 12-hour nicotine abstinence period, subjects will be instructed to chew the gum once every 2 seconds, for 30 minutes.<br>* Other names: Nicorette®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration | The maximum observed nicotine concentration in plasma (Cmax) | Baseline to 10 hours post-dose | 
| Area under the Curve | The area under the plasma concentration-vs.-time curve until the last measurable concentration (AUCt)and the area under the plasma concentration-vs.-time curve until infinity (AUC∞) | 10 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Concentration | Time to Maximum Concentration (Tmax) | 10 hours post-dose | 
| Residual Nicotine | The amount of residual nicotine in the product after being chewed. | 30 minutes | 
| Dissolution Time | Actual time required for oral dissolution of new NRT products following product administration | 10 hours post-dose | 

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