Single-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product

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

Detailed Description
-----------------
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 nicotine pharmacokinetics, during 12 hours after start of administration. Single doses of each treatment are given once in the morning during five separate treatment visits scheduled in a crossover setting with randomized treatment sequences. The study will include 45 healthy smokers between 18-50 years, who have been smoking at least 15 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
-----------------
Single-dose Nicotine Pharmacokinetics With a New Oral Nicotine Replacement Product. A Study in Healthy Smokers

Conditions
-----------------
Tobacco Dependence

Intervention / Treatment
-----------------
* Drug: Oral Nicotine
* Drug: NiQuitinTM Nicotine Lozenge
* Drug: Nicorette® Nicotine Gum


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy smokers, smoking at least 15 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 months preceding the first dose of study medication.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 1<br>One oral administration of 1 mg nicotine | Drug: Oral Nicotine<br>* A new l mg oral nicotine product<br>* Other names: Experimental nicotine 1 mg;|
| Experimental: Oral Nicotine 2<br>Two oral administrations of 1 mg nicotine | Drug: Oral Nicotine<br>* A new l mg oral nicotine product<br>* Other names: Experimental nicotine 1 mg;|
| Experimental: Oral Nicotine 4<br>Four oral administrations of 1 mg nicotine | Drug: Oral Nicotine<br>* A new l mg oral nicotine product<br>* Other names: Experimental nicotine 1 mg;|
| Active Comparator: NiQuitinTM Nicotine Lozenge 4 mg<br>One 4 mg marketed nicotine lozenge | Drug: NiQuitinTM Nicotine Lozenge<br>* A marketed 4 mg Nicotine lozenge<br>* Other names: NiQuitinTM lozenge;|
| Active Comparator: Nicorette® Gum 4 mg<br>One marketed Nicorette® nicotine gum 4 mg chewed for 30 minutes | Drug: Nicorette® Nicotine Gum<br>* A marketed 4 mg Nicotine Gum<br>* Other names: Nicorette® gum;|

What is the study measuring?
-----------------
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 12 hours after start of administration | 
| Bioavailability | A measure of how much of the drug reaches a person's bloodstream within a given period of time for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The area under the curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period to form a curve. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour*nanograms/milliliter (h*ng/ml). | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Plasma Concentration | Area under the nicotine plasma concentration curve at 10 minutes (AUC10 min) | During 10 minutes after start of administration | 
| Time of Maximum Concentration | The time at which maximum concentration is reached (Tmax) | During 12 hours after start of administration | 
| Terminal Elimination Rate Constant | The terminal nicotine elimination rate constant (Lamda z) | During 12 hours after start of administration | 
| Released Nicotine | The amount of nicotine released from Nicorette® gum 4 mg during 30 minutes' chewing | After 30 minutes' chewing | 

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