A Study to Assess the Nicotine Pharmacokinetics, Tolerability and Safety With a New Oral Nicotine Replacement Product in Healthy Japanese Smokers

May 4, 2018 updated by: Janssen Pharmaceutical K.K.

A Single-dose and Repeated-dose, Open-label, Randomized, Cross-over Study to Assess the Nicotine Pharmacokinetics, Tolerability and Safety With A New Oral Nicotine Replacement Product in Healthy Japanese Smokers.

In Part 1, the purpose of this study is to elucidate the single-dose pharmacokinetic profiles of 1 spray and 2 consecutive sprays of oromucosal nicotine spray (ONS) in comparison with those of nicotine gum and cigarette smoking in healthy Japanese smokers. In Part 2, the purpose is to evaluate the multiple-dose nicotine pharmacokinetics of ONS administered repeated-dose administration in healthy Japanese smokers.

Study Overview

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Fukuoka, Japan, 8120025
        • Souseikai Hakata Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy male or female Japanese participants between the ages of 20 and 50 years, inclusive. Health is defined as the absence of clinically relevant abnormalities identified by a detailed medical history, blood pressure, pulse rate measurements, 12-lead electrocardiogram (ECG) as well as clinical laboratory tests, as judged by the principal investigator or sub investigator.
  • Smoking of at least 15 cigarettes daily during at least one year preceding inclusion
  • Body Mass Index between 17.5 and 30.0 kilogram per square meter (kg/m^2) and a total body weight greater than or equal to (>=) 50.0 kg
  • Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
  • All women of childbearing potential, except for postmenopausal females, must have a negative urine beta-human chorionic gonadotropin (beta-hCG) at screening of Part 1 and all planned visits of Part 1 and Part 2

Exclusion Criteria:

  • Evidence or history of an acute or chronic medical or psychiatric condition or allergy or laboratory abnormality, or of use of drugs that, in the judgment of the principal investigator or sub investigator, increase the risk associated with study participation or interfere with the interpretability of study results
  • Females: Pregnancy, breast-feeding, premenopausal, or perimenopausal state with insufficient contraception
  • Treatment with an investigational drug within 3 months preceding the first dose of study product
  • Participant has donated blood or blood product or had substantial loss of blood more than 200 milliliter (mL) within 1 month before study products administration, or greater than or equal to (>=) 400 mL within 3 months for males and 4 months for females before study products administration, or participant has donated a total volume of blood in the past one year exceeding 1,200 mL for males and 800 mL for females, or participant has an intention to donate blood or blood products during the study and for at least 3 months for males and 4 months for females for blood, or at least 2 months for both genders for blood products after completion of the study
  • Exclusion Criterion for Only Part 2: participants who is analyzed as cytochrome (CYP)2A6 *4/*4 by CYP2A6 genetic polymorphism test at Visit 1 of Part 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part 1; Treatment Sequence ABDC
Participants will receive Treatment A (one spray of oromucosal nicotine spray [ONS]) at Visit 1, then Treatment B (2 consecutive sprays of ONS at Visit 2, then Treatment D (1 cigarette [10 puffs]) at Visit 3, followed by Treatment C (nicotine gum) at Visit 4. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).
Participants will chew nicotine gum for 30 minutes.
Participants will smoke one cigarette as 10 puffs for 3 minutes.
EXPERIMENTAL: Part 1; Treatment Sequence BCAD
Participants will receive Treatment B at Visit 1, then Treatment C at Visit 2, then Treatment A at Visit 3 followed by Treatment D at Visit 4. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).
Participants will chew nicotine gum for 30 minutes.
Participants will smoke one cigarette as 10 puffs for 3 minutes.
EXPERIMENTAL: Part 1; Treatment Sequence CDBA
Participants will receive Treatment C at Visit 1, then Treatment D at Visit 2, then Treatment B at Visit 3 followed by Treatment A at Visit 4. The visits will be separated by a period of at least 7 calendar days. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).
Participants will chew nicotine gum for 30 minutes.
Participants will smoke one cigarette as 10 puffs for 3 minutes.
EXPERIMENTAL: Part 1; Treatment Sequence DACB
Participants will receive Treatment D at Visit 1, then Treatment A at Visit 2, then Treatment C at Visit 3 followed by Treatment B at Visit 4. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).
Participants will chew nicotine gum for 30 minutes.
Participants will smoke one cigarette as 10 puffs for 3 minutes.
EXPERIMENTAL: Part 2; Treatment Sequence EF
Participants who complete Part 1 will be selected for Part 2 based on the results of genetic polymorphism test and other examinations. Selected participants will receive Treatment E (two consecutive sprays of ONS once every 30 minutes until 11.5 hours) at Visit 5, followed by Treatment F (two consecutive sprays of ONS once every 1 hour until 11 hours) at Visit 6. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).
EXPERIMENTAL: Part 2; Treatment Sequence FE
Participants who complete Part 1 will be selected for Part 2 based on the results of genetic polymorphism test and other examinations. Selected participants will receive Treatment F at Visit 5 followed by Treatment E at Visit 6. The visits will be separated by a period of at least 7 calendar days.
Participants will receive oral dose of oromucosal nicotine spray (ONS).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Maximum Baseline Corrected Plasma Nicotine Concentration (cCmax)
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 minute (min) and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
cCmax is defined as the maximum baseline corrected plasma nicotine concentration (cCmax).
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 minute (min) and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration versus (vs) Time Curve Until the Last Measurable Time Point (cAUCt)
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
cAUCt is defined as the baseline corrected area under the plasma nicotine concentration-vs time curve until the last measurable time point.
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve Extrapolated to Infinite (cAUC[infinity])
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
cAUC(infinity) is defined as the baseline corrected area under the plasma nicotine concentration-vs time curve extrapolated to infinite.
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve until the Last Measurable Time Point (cAUCt)
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
cAUCt is defined as baseline corrected area under the plasma nicotine concentration-vs time curve until the last measurable time point.
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 2: Average Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cav)
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Cav is defined as the average plasma nicotine concentration during the last dosing interval/intervals.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 2: Area Under the Plasma Nicotine Concentration-vs Time Curve During the Last Dosing Interval/Intervals (AUCtau)
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
AUCtau is defined as the area under the plasma nicotine concentration-vs time curve during the last dosing interval/intervals.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 2: Maximum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmax)
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Cmax is defined as maximum observed plasma nicotine concentration.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Area Under the Plasma Nicotine Concentration-vs Time Curve until 10 Minutes after Start of Administration [AUC10min],
Time Frame: Predose; 2, 4, 6, 8, 10 min postdose
AUC10min is defined as the area under the plasma nicotine concentration-vs time curve until 10 minutes after start of administration.
Predose; 2, 4, 6, 8, 10 min postdose
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 1: Terminal Half-Life [t1/2]
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Terminal half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 1: Terminal Elimination Rate Constant (Lambda[z])
Time Frame: Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Lambda (z) is apparent terminal elimination rate constant, determined by linear regression using the terminal log-linear phase of the log transformed concentration-time curve.
Predose; 2, 4, 6, 8, 10, 15, 20, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Part 2: Minimum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmin)
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Cmin is defined as the minimum plasma nicotine concentration during the last dosing interval/intervals.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 2: Peak-Trough Fluctuation [PTF]
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
PTF calculated by 100*(Cmax - Cmin)/Cav will be assessed.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 2: Swing
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Swing will be calculated as (Cmax - Cmin)/Cmin.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Predose, 2, 4, 6, 8, 10, 15, 20, 30 post last dose (last dose: Hour 11.5 for Treatment E and Hour 11 for Treatment F); 45 and 60 min post last dose for Treatment F
Part 1 and Part 2: Number of Participants with Adverse Events (AEs)
Time Frame: Up to 4 months
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Up to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 22, 2017

Primary Completion (ACTUAL)

April 16, 2018

Study Completion (ACTUAL)

April 16, 2018

Study Registration Dates

First Submitted

December 22, 2017

First Submitted That Met QC Criteria

January 11, 2018

First Posted (ACTUAL)

January 16, 2018

Study Record Updates

Last Update Posted (ACTUAL)

May 7, 2018

Last Update Submitted That Met QC Criteria

May 4, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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