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

Healthy Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03398876
• Other study ID #: CR108422
• Secondary ID: 10258820TDP1001
• Status: Completed
• Phase: Phase 1
• Start date: December 22, 2017
• Est. completion date: April 16, 2018

Study information

• Verified date: May 2018
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 16, 2018
• Est. primary completion date: April 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Oromucosal Nicotine Spray (ONS)
Participants will receive oral dose of oromucosal nicotine spray (ONS).
• Nicotine Gum
Participants will chew nicotine gum for 30 minutes.

Other:
• Cigarette
Participants will smoke one cigarette as 10 puffs for 3 minutes.

Locations

Country	Name	City	State
Japan	Souseikai Hakata Clinic	Fukuoka

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Maximum Baseline Corrected Plasma Nicotine Concentration (cCmax)	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
Primary	Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration versus (vs) Time Curve Until the Last Measurable Time Point (cAUCt)	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
Primary	Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve Extrapolated to Infinite (cAUC[infinity])	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
Primary	Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve until the Last Measurable Time Point (cAUCt)	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
Primary	Part 2: Average Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cav)	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
Primary	Part 2: Area Under the Plasma Nicotine Concentration-vs Time Curve During the Last Dosing Interval/Intervals (AUCtau)	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
Primary	Part 2: Maximum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmax)	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	Part 1: Area Under the Plasma Nicotine Concentration-vs Time Curve until 10 Minutes after Start of Administration [AUC10min],	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
Secondary	Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax)	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
Secondary	Part 1: Terminal Half-Life [t1/2]	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
Secondary	Part 1: Terminal Elimination Rate Constant (Lambda[z])	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
Secondary	Part 2: Minimum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmin)	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
Secondary	Part 2: Peak-Trough Fluctuation [PTF]	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
Secondary	Part 2: Swing	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
Secondary	Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax)	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
Secondary	Part 1 and Part 2: Number of Participants with Adverse Events (AEs)	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