Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 (THS 2.2)

A Single-center, Open-label, Randomized, Controlled, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile and Safety of THS 2.2 Following Single Use in Healthy Smokers Compared to Conventional Cigarettes and Nicotine Gum

The overall goal of the study is to evaluate the pharmacokinetic (PK) profile (rate and the amount of nicotine absorbed) following a single use of the THS 2.2, a candidate Modified Risk Tobacco Product, compared to the PK profiles from a single use of a cigarette (CC) and from a single use of nicotine gum in a Japanese population.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: THS 2.2; Other: CC; Other: NRT Gum

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 184-0005
    • Koganeibashi Sakura Clinic, 2-11-25, Sakuracho, Koganei-shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is Japanese.
• Smoking, healthy subject as judged by the Investigator.
• Subject smokes at least 10 commercially available CCs per day (no brand restrictions) for the last 4 weeks.
• Subject does not plan to quit smoking in the next 3 months.

Exclusion Criteria:

• As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).
• Subject has received medication within 14 days or within 5 half-lives of a drug (whichever is longer) which has an impact on CYP2A6 activity.
• Female subject is pregnant or breast feeding.
• Female subject does not agree to use an acceptable method of effective contraception.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: THS 2.2 then CC; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of THS 2.2); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of CC).	Other: THS 2.2; Single use of the Tobacco Heating System 2.2 (THS 2.2); Other: CC; Single use of subject's own cigarette (CC)
Active Comparator: CC then THS 2.2; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of CC); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of THS 2.2).	Other: THS 2.2; Single use of the Tobacco Heating System 2.2 (THS 2.2); Other: CC; Single use of subject's own cigarette (CC)
Active Comparator: THS 2.2 then NRT; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of THS 2.2); Day 2 = wash-out; Day 3 = 2nd intervention (single administration of NRT gum [Nicorette® 2mg]).	Other: THS 2.2; Single use of the Tobacco Heating System 2.2 (THS 2.2); Other: NRT Gum; Single administration of the nicotine replacement therapy (NRT) 2 mg gum (Nicorette® 2mg)
Active Comparator: NRT then THS 2.2; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single administration of NRT gum [Nicorette® 2mg]); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of THS 2.2).	Other: THS 2.2; Single use of the Tobacco Heating System 2.2 (THS 2.2); Other: NRT Gum; Single administration of the nicotine replacement therapy (NRT) 2 mg gum (Nicorette® 2mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Nicotine Following Single Use of THS 2.2, CC and NRT	T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided.	Blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0
Area Under the Plasma Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of THS 2.2, CC and NRT	T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided.	Blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Masayuki Sugimoto, MD PhD, Koganeibashi Sakura Clinic

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 8, 2013
• First Submitted That Met QC Criteria: October 9, 2013
• First Posted (Estimate): October 10, 2013

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Smoking; Cigarettes; Nicotine absorption; Candidate modified risk tobacco product; Nicotine Replacement Therapy gum (NRT gum)
• Other Study ID Numbers: ZRHR-PK-02-JP (Other Identifier: Philip Morris Products S.A.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO