Multiple-dose Nicotine Pharmacokinetics With Three Oral Nicotine Replacement Products

Multiple-dose Nicotine Pharmacokinetics With Three Oral Nicotine Replacement Products. A Study in Healthy Smokers.

Multiple-dose nicotine pharmacokinetics with three oral nicotine replacement products. A study in healthy smokers.

Study Overview

• Status: Completed
• Conditions: Tobacco Dependence
• Intervention / Treatment: Drug: Nicotine; Drug: Nicotine; Drug: Nicotine

Detailed Description

Fifty (50) healthy male or female subjects between the ages of 19 and 50 years, inclusive, smoking at least 20 cigarettes daily during at least one year preceding inclusion. Multiple doses of all study treatments are given either every 60 minutes or every 90 minutes, respectively. All products will be administered in accordance with labeling, on five separate treatment visits. The subjects will abstain from smoking from 8 pm in the evening before and until the end of each visit.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

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

Description

Inclusion Criteria:

• Healthy subjects, smoking at least 20 cigarettes daily during at least one year preceding inclusion.
• BMI between 17.5 and 30.0 kg/m2 and a total body weight of at least 55.0 kg.
• 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.
• Willing and able to comply with all scheduled visits and study procedures

Exclusion Criteria:

• Pregnancy, lactation or intended pregnancy.
• Treatment with an investigational product or donation or loss of blood within 3 month preceding the first dose of study medication.
• Any medical condition or history that might, per protocol or in the opinion of the investigator, compromise subject safety or trial results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NRT 60; A 6 mg dose of an experimental Nicotine Replacement Therapy (NRT) given every hour for 11 hours, with a 36-hour washout between visits	Drug: Nicotine; 6 mg experimental Nicotine Replacement Therapy (NRT); Other Names: Not yet marketed; Drug: Nicotine; 4 mg marketed Nicotine Fruit Gum (NFG); Other Names: Nicorette® Freshfruit Gum; Drug: Nicotine; 4 mg marketed nicotine mint lozenge (NIQ); Other Names: NiQuitinTM Mint lozenge
Active Comparator: NFG 60; A 4 mg dose of a marketed Nicotine Fruit Gum (NFG) given every hour for 11 hours, with a 36-hour washout between visits	Drug: Nicotine; 6 mg experimental Nicotine Replacement Therapy (NRT); Other Names: Not yet marketed; Drug: Nicotine; 4 mg marketed Nicotine Fruit Gum (NFG); Other Names: Nicorette® Freshfruit Gum; Drug: Nicotine; 4 mg marketed nicotine mint lozenge (NIQ); Other Names: NiQuitinTM Mint lozenge
Experimental: NRT 90; A 6 mg dose of NRT given every 90 minutes for 10.5 hours, with a 36-hour washout between visits	Drug: Nicotine; 6 mg experimental Nicotine Replacement Therapy (NRT); Other Names: Not yet marketed; Drug: Nicotine; 4 mg marketed Nicotine Fruit Gum (NFG); Other Names: Nicorette® Freshfruit Gum; Drug: Nicotine; 4 mg marketed nicotine mint lozenge (NIQ); Other Names: NiQuitinTM Mint lozenge
Active Comparator: NFG 90; A 4 mg dose of NFG given every 90 minutes for 10.5 hours, with a 36-hour washout between visits	Drug: Nicotine; 6 mg experimental Nicotine Replacement Therapy (NRT); Other Names: Not yet marketed; Drug: Nicotine; 4 mg marketed Nicotine Fruit Gum (NFG); Other Names: Nicorette® Freshfruit Gum; Drug: Nicotine; 4 mg marketed nicotine mint lozenge (NIQ); Other Names: NiQuitinTM Mint lozenge
Active Comparator: NIQ 60; A 4 mg dose of marketed nicotine mint lozenge (NIQ), given every hour for 11 hours, with a 36-hour washout between visits	Drug: Nicotine; 6 mg experimental Nicotine Replacement Therapy (NRT); Other Names: Not yet marketed; Drug: Nicotine; 4 mg marketed Nicotine Fruit Gum (NFG); Other Names: Nicorette® Freshfruit Gum; Drug: Nicotine; 4 mg marketed nicotine mint lozenge (NIQ); Other Names: NiQuitinTM Mint lozenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration	Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma within the last dosing interval, measured in nanograms/milliliter (ng/mL)	within the last dosing interval (starting at 10.5-11 hours after first product administration)
Average Concentration	Average Nicotine Plasma Concentration (Cav) within the last dosing interval	within the last dosing interval (starting at 10.5-11 hours after first product administration)
Area Under the Curve	Area under the nicotine plasma concentration-vs.-time curve during the last dosing interval (AUCt)	within the last dosing interval (starting at 10.5-11 hours after first product administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Maximum Concentration	The time at which maximum concentration is reached (Tmax)	During 12 hours post-dose
Minimum Observed Concentration	Minimum Observed Plasma Concentration (Cmin), which is the minimum concentration (amount of drug) measurable in blood plasma within the last dosing interval, measured in nanograms/milliliter (ng/mL)	within the last dosing interval (starting at 10.5-11 hours after first product administration)
Peak-Trough Fluctuation	Percent of Peak-Trough Fluctuation in one dosing interval at steady state (PTF)	within the last dosing interval (starting at 10.5-11 hours after first product administration)
Swing	Swing in one dosing interval at steady state, calculated as (Cmax-Cmin)/ Cmin	within the last dosing interval (starting at 10.5-11 hours after first product administration)
Nicotine Released	The amount of nicotine released from the product during product administration	30 minutes

Collaborators and Investigators

• Sponsor: McNeil AB

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimate): March 24, 2011

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: NICTDP1081; 2010-023026-20 (EudraCT Number)