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

NCT03398876 | Completed Phase 1

• 2 other identifiers: CR10842210258820TDP1001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (9)

• Part 1: Area Under the Plasma Nicotine Concentration-vs Time Curve until 10 Minutes after Start of Administration [AUC10min],

  Predose; 2, 4, 6, 8, 10 min postdose

• Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax)

  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]

  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])

  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)

  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

Study Arms (6)

Part 1; Treatment Sequence ABDC

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS); Drug: Nicotine Gum; Other: Cigarette

Part 1; Treatment Sequence BCAD

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS); Drug: Nicotine Gum; Other: Cigarette

Part 1; Treatment Sequence CDBA

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS); Drug: Nicotine Gum; Other: Cigarette

Part 1; Treatment Sequence DACB

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS); Drug: Nicotine Gum; Other: Cigarette

Part 2; Treatment Sequence EF

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS)

Part 2; Treatment Sequence FE

EXPERIMENTAL

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.

Drug: Oromucosal Nicotine Spray (ONS)

Interventions

Oromucosal Nicotine Spray (ONS) DRUG

Participants will receive oral dose of oromucosal nicotine spray (ONS).

Part 1; Treatment Sequence ABDC; Part 1; Treatment Sequence BCAD; Part 1; Treatment Sequence CDBA; Part 1; Treatment Sequence DACB; Part 2; Treatment Sequence EF; Part 2; Treatment Sequence FE

Nicotine Gum DRUG

Participants will chew nicotine gum for 30 minutes.

Part 1; Treatment Sequence ABDC; Part 1; Treatment Sequence BCAD; Part 1; Treatment Sequence CDBA; Part 1; Treatment Sequence DACB

Cigarette OTHER

Participants will smoke one cigarette as 10 puffs for 3 minutes.

Part 1; Treatment Sequence ABDC; Part 1; Treatment Sequence BCAD; Part 1; Treatment Sequence CDBA; Part 1; Treatment Sequence DACB

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (1)

Souseikai Hakata Clinic

Fukuoka, 8120025, Japan

Location

MeSH Terms

Interventions

Nicotine Chewing Gum; Tobacco Products

Intervention Hierarchy (Ancestors)

Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Tobacco Use Cessation Devices; Therapeutics; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 16, 2018
• Study Start: December 22, 2017
• Primary Completion: April 16, 2018
• Study Completion: April 16, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

JP (1)