Pharmacokinetic Study of 4 mg Nicotine Lozenge.

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Prototype 1	nicotine	4mg nicotine lozenge administered orally as a single dose treatment per subject
Prototype 2	nicotine	4mg nicotine lozenge administered orally as a single dose treatment per subject
Prototype 3	nicotine	4mg nicotine lozenge administered orally as a single dose treatment per subject
Reference Therapy	nicotine	4mg nicotine lozenge (internationally marketed) to be administered orally as a single dose treatment per subject.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time 0 to t, AUC (0-t)	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	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.
Maximum Plasma Concentration (Cmax)	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 nicotine concentration was determined from plasma-concentration time profiles. Cmax was based on the baseline adjusted nicotine plasma concentration data.

Secondary Outcome Measures

Name	Time	Method
Rate of Elimination (Kel)	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	Elimination rate constant for nicotine was calculated. Kel was based on the baseline adjusted nicotine plasma concentration data.
Plasma Half Life (t1/2)	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	Half-life of elimination of nicotine was determined. t1/2 was based on the baseline adjusted nicotine plasma concentration data.
Time to Maximum Plasma Concentration (Tmax)	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	Tmax was determined from plasma concentration time profiles. Tmax was based on the baseline adjusted nicotine plasma concentration data.
AUC(0-inf)	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	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.