Pharmacokinetics of Nicotine Sublingual Tablets Versus Nicorette Lozenge in Healthy Smokers
Condition: Tobacco Use Disorder; Cigarette Smoking
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to compare two different dosage forms from which nicotine is
      released and absorbed into the bloodstream.
    

Detailed description: 
      Objective The primary objective of this study is to determine the pharmacokinetic profile of
      a single dose of Nicotine Sublingual Tablets, 4 mg (Test Product) versus Nicorette Lozenge 4
      mg in healthy adult smokers when administered under fasted conditions.

      Study Design This is an open-label, pseudorandomized, two-way crossover comparison of the 4
      mg sublingual nicotine tablet versus the Nicorette Lozenge 4 mg.

      Number of Subjects Twenty-four (24) healthy adult smokers will be enrolled. Screening
      Procedures Demographic data, medical and medication histories, physical examination,
      measurement of height and weight, electrocardiogram (ECG), vital signs (blood pressure, heart
      rate, body temperature and respiratory rate), hematology, chemistry, urinalysis, end-expired
      Carbon Monoxide, and serum pregnancy test (for female subjects only) .

      Confinements Subjects will be confined approximately 2 hours or earlier prior to study drug
      administration until after discharge vital signs and the 240 minute (min) post-dose blood
      draw and End-of-Study (EOS) procedures.

      Study Drug Administration A single dose of Test Product (Nicotine Sublingual Tablets, 4 mg)
      and Nicorette Lozenge 4 mg will be administered to each subject in the study.

      Sample Collection A total of 14 blood samples will be obtained per period. Samples will be
      taken pre-dose (up to 90 minutes prior to dose) and 3, 6, 9, 12, 15, 20 30, 45, 60, 90, 120,
      180 and 240 minutes post-dose. A minimum of 48 hours will transpire between dose
      administrations.

      Safety Assessments Vital signs (blood pressure, heart rate, body temperature and respiratory
      rate) will be measured before administration of study drug. The following will be performed
      at check-in: urine pregnancy test (for female subjects only). Ongoing monitoring for adverse
      events (AEs) will be performed during the study. Prior to release from the clinic, a
      well-being assessment and discharge vital signs will be completed 240 minutes (±60 min) post
      dosing or at Early Termination (ET).

      End of Study (EOS) or Early Termination (ET) Procedures Vital signs and monitoring for AEs
      will be done 240 min post-dosing or at ET/withdrawal prior to release from clinic.

      Analytical Method Plasma concentrations of nicotine will be determined using a validated
      liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.

      Pharmacokinetics/Pharmacodynamics Determination of primary parameters Area under the curve (
      AUC0-t, AUC0-inf), concentration maximum (Cmax), Time to maximum concentration(Tmax) and
      secondary parameters such as plasma elimination half-life( t1/2) using a by non-linear
      kinetics program (WinNonlin®). Pharmacodynamics effects will be measured by taking the heart
      rate and blood pressure will be taken three times in the first 30 minutes after test product
      administration. A craving assessment will be obtained at 1, 3, 7, 11, and 14 minutes
      post-medication administration.

      Statistical Analyses No formal statistical analyses are planned; descriptive statistics of
      the concentration and pharmacokinetic data on nicotine will be provided. Exploratory analyses
      of craving reductions will be conducted.
    

Intervention name(s): Sublingual tablet 4 mg versus Nicorette Lozenge 4mg
Intervention type(s): Drug
Intervention description(s): One dose of study drug (sublingual tablet or Nicorette Lozenge) will be administered to each subject in the morning on Day 1.
The second administration of drug will occur at least 48 hours after the initial administration. Subjects will receive the other dosage form and be instructed according to whether they are receiving the sublingual tablet or the lozenge.
Other intervention name(s): Pharmacokinetic comparison of two nicotine dosage forms
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: pharmacokinetics; nicotine absorption