Clinical trial NCT03398876: A Study to Assess the Nicotine Pharmacokinetics, Tolerability and Safety With a New Oral Nicotine Replacement Product in Healthy Japanese Smokers
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2018-01-16
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Maximum Baseline Corrected Plasma Nicotine Concentration (cCmax)
timeFrame: 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
measure: Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration versus (vs) Time Curve Until the Last Measurable Time Point (cAUCt)
timeFrame: 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
measure: Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve Extrapolated to Infinite (cAUC[infinity])
timeFrame: 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
measure: Part 1: Baseline Corrected Area Under the Plasma Nicotine Concentration-vs Time Curve until the Last Measurable Time Point (cAUCt)
timeFrame: 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
measure: Part 2: Average Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cav)
timeFrame: 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
measure: Part 2: Area Under the Plasma Nicotine Concentration-vs Time Curve During the Last Dosing Interval/Intervals (AUCtau)
timeFrame: 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
measure: Part 2: Maximum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmax)
timeFrame: 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 outcomes:
measure: Part 1: Area Under the Plasma Nicotine Concentration-vs Time Curve until 10 Minutes after Start of Administration [AUC10min],
timeFrame: Predose; 2, 4, 6, 8, 10 min postdose
measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Part 1: Terminal Half-Life [t1/2]
timeFrame: 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
measure: Part 1: Terminal Elimination Rate Constant (Lambda[z])
timeFrame: 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
measure: Part 2: Minimum Plasma Nicotine Concentration During the Last Dosing Interval/Intervals (Cmin)
timeFrame: 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
measure: Part 2: Peak-Trough Fluctuation [PTF]
timeFrame: 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
measure: Part 2: Swing
timeFrame: 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
measure: Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 4 months
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Souseikai Hakata Clinic
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: