Pharmacokinetic Study of 4 mg Nicotine Lozenge.

Study Overview
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Brief Summary
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This is a randomized, single center, open label, single dose, four way crossover study in fasted healthy male subjects to compare the pharmacokinetics of nicotine following administration of 3 prototype 4mg nicotine lozenge to an internationally marketed 4mg nicotine lozenge. Blood samples will be drawn at pre-specified intervals for a total of 12 hours post dose in each treatment session and plasma samples analyzed for nicotine levels.

Official Title
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A Randomized, Cross-Over, Single Dose Pharmacokinetic Study of 4mg Nicotine Lozenges.

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - smoked commercially-manufactured cigarettes daily for the preceding 12 months and routinely smokes first cigarette within 30mins of awakening. Exclusion Criteria: inability to refrain from smoking during confinement period, smoking tobacco in any other form other than commercially manufactured cigarettes, subject has used chewing tobacco or other tobacco products other than commercially manufactured cigarettes within 7 days of dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Prototype 1<br>4mg nicotine lozenge administered orally as a single dose treatment per subject | Drug: nicotine<br>* 4 mg nicotine lozenge experimental<br>|
| Experimental: Prototype 2<br>4mg nicotine lozenge administered orally as a single dose treatment per subject | Drug: nicotine<br>* 4 mg nicotine lozenge experimental<br>|
| Experimental: Prototype 3<br>4mg nicotine lozenge administered orally as a single dose treatment per subject | Drug: nicotine<br>* 4 mg nicotine lozenge experimental<br>|
| Active Comparator: Reference Therapy<br>4mg nicotine lozenge (internationally marketed) to be administered orally as a single dose treatment per subject. | Drug: nicotine<br>* 4 mg nicotine lozenge experimental<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time 0 to t, AUC (0-t) | Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined from plasma concentration time profile of nicotine. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | 
| Maximum Plasma Concentration (Cmax) | Maximum plasma nicotine concentration was determined from plasma-concentration time profiles. Cmax was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-inf) | Area under the plasma nicotine concentration-time curve from zero extrapolated to infinity was determined. AUC(0-inf) was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | 
| Time to Maximum Plasma Concentration (Tmax) | Tmax was determined from plasma concentration time profiles. Tmax was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | 
| Rate of Elimination (Kel) | Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing | 
| Plasma Half Life (t1/2) | Half-life of elimination of nicotine was determined. t1/2 was based on the baseline adjusted nicotine plasma concentration data. | Blood samples were collected pre-dose and at 5, 10, 15, 30 and 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post dosing |