Bioequivalence Between Two Oral Nicotine Sublingual Tablets, 2 mg and 4 mg

Study Overview
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Brief Summary
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The purpose of this study is to assess the bioequivalence between two oral nicotine sublingual tablets, 2 mg and 4 mg.

Detailed Description
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The study is a single-dose, randomized, 2 x two-way cross-over study. The investigational products will be given as single doses at separate visits. Periods without Nicotine Replacement Therapy (NRT), lasting for at least 36 hours, will separate treatment visits. Blood will be sampled at each treatment visit for pharmacokinetic analyses pre-dose, and at 5, 10, 15, 20, 30, and 45 minutes, as well as 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 10 hours after start of product administration. The time until complete product dissolution will be recorded. Subjects will also be monitored to capture any adverse events that may occur. The trial is open in the sense that subjects and study personnel will be aware of what product is administered at a given visit. However, the treatment labels will not be known by the people performing bioanalysis or analyzing pharmacokinetic data.

Official Title
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Bioequivalence Between Two Oral Nicotine Sublingual Tablets, 2 mg and 4 mg - A Study in Healthy Smokers

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Nicotine Sublingual Tablet Mint (NSTM)
* Drug: Marketed Nicotine Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, smoking at least 10 cigarettes daily during at least one year preceding inclusion and Body Mass Index (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
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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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotine Sublingual Tablet Mint (NSTM)-2<br>Experimental 2 mg NSTM | Drug: Nicotine Sublingual Tablet Mint (NSTM)<br>* A single dose of an experimental NSTM, with a 36-hour washout between visits<br>* Other names: Not marketed;|
| Active Comparator: Microtab-2<br>2 mg Nicotine tablet | Drug: Marketed Nicotine Tablet<br>* A single dose of a marketed Nicotine Replacement Therapy (NRT), with a 36-hour washout between visits<br>* Other names: Nicorette® Microtab;|
| Experimental: NSTM-4<br>Experimental 4 mg Nicotine Sublingual Tablet Mint | Drug: Nicotine Sublingual Tablet Mint (NSTM)<br>* A single dose of an experimental NSTM, with a 36-hour washout between visits<br>* Other names: Not marketed;|
| Active Comparator: Microtab-4<br>2 x 2 mg Nicotine tablet | Drug: Marketed Nicotine Tablet<br>* A single dose of a marketed Nicotine Replacement Therapy (NRT), with a 36-hour washout between visits<br>* Other names: Nicorette® Microtab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax, which is the maximum observed plasma concentration after a dose is administered, measured in nanograms/milliliter (ng/mL) | During 10 hours post-dose | 
| Area Under the Curve (AUC)(0-t) | Bioavailability within the Set Period [AUC(0-t)] is the area under the plasma concentration verses time curve from start of drug administration until the time of the last measurable plasma concentration, calculated as hour * nanograms (ng) per milliliter (mL). | During 10 hours post-dose | 
| AUC(0-∞) | AUC (0-∞) is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. It is obtained from calculating AUC (0-t) plus AUC (t-∞). | 10 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Product Dissolution Time | Product Dissolution Time is the time from administration until the investigational products were completely dissolved. | During 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