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

A Single-center, Open-label, Randomized, Controlled, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile and Safety of Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) Following Single Use in Smoking, Healthy Subjects Compared to Menthol Conventional Cigarettes and Nicotine Gum.

The primary objective of this clinical study is to evaluate the pharmacokinetic (PK) profile (rate and amount of nicotine absorbed) following a single use of the THS 2.2 Menthol (mTHS), a candidate Modified Risk Tobacco Product, compared to the PK profiles from a single use of a menthol cigarette (mCC) and from a single use of nicotine replacement therapy gum (NRT).

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: mTHS; Other: mCC; Other: NRT

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Saitama, Japan, 362 0021
    • Ageo Medical Clinic, 3133 Haraichi, Ageo-shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is Japanese.
• Smoking, healthy subject as judged by the Investigator.
• Subject has smoked at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks.
• Subject has smoked for at least the last 3 consecutive years.
• 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 medication (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: mTHS then mCC; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of mTHS); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of mCC).	Other: mTHS; Single use of Tobacco Heating System 2.2 Menthol (mTHS); Other: mCC; Single use of subject's own menthol cigarette (mCC)
Active Comparator: mCC then mTHS; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of mCC); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of mTHS).	Other: mTHS; Single use of Tobacco Heating System 2.2 Menthol (mTHS); Other: mCC; Single use of subject's own menthol cigarette (mCC)
Active Comparator: mTHS then NRT; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single product use of mTHS); Day 2 = wash-out; Day 3 = 2nd intervention (single administration of NRT)	Other: mTHS; Single use of Tobacco Heating System 2.2 Menthol (mTHS); Other: NRT; Single administration of 2 mg gum (Nicorette® 2mg)
Active Comparator: NRT then mTHS; Each subject will follow the below study design: Day 0 = Wash-out (1 day); Day 1 = 1st intervention (single administration of NRT); Day 2 = wash-out; Day 3 = 2nd intervention (single product use of mTHS).	Other: mTHS; Single use of Tobacco Heating System 2.2 Menthol (mTHS); Other: NRT; Single administration of 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 mTHS, mCC 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 mTHS, mCC 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: Fumimasa Nobuoka, MD, Ageo Medical Clinic

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Smoking; Cigarette; Nicotine absorption; Candidate modified risk tobacco product; Nicotine replacement therapy; Nicotine gum
• Other Study ID Numbers: ZRHM-PK-05-JP (Other Identifier: Philip Morris Products S.A.)

Plan for Individual participant data (IPD)

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