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

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

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

Study Overview

• Status: Completed
• Conditions: Tobacco Dependence
• Intervention / Treatment: Drug: Nicotine Sublingual Tablet Mint (NSTM); Drug: Marketed Nicotine Tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, SE-222 20
    • McNeil AB Clinical Pharmacology R&D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McNeil AB

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: November 9, 2010
• First Submitted That Met QC Criteria: November 9, 2010
• First Posted (Estimate): November 10, 2010

Study Record Updates

• Last Update Posted (Estimate): July 10, 2012
• Last Update Submitted That Met QC Criteria: July 6, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Smoking Cessation; Nicotine pharmacokinetics
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: NICTDP1064-A6431115; 2007-002180-27 (EudraCT Number)