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

Study Overview
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Brief Summary
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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).

Official Title
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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.

Conditions
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Smoking

Intervention / Treatment
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* Other: mTHS
* Other: mCC
* Other: NRT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: mTHS then mCC<br>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<br>* Single use of Tobacco Heating System 2.2 Menthol (mTHS)<br>Other: mCC<br>* Single use of subject's own menthol cigarette (mCC)<br>|
| Active Comparator: mCC then mTHS<br>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<br>* Single use of Tobacco Heating System 2.2 Menthol (mTHS)<br>Other: mCC<br>* Single use of subject's own menthol cigarette (mCC)<br>|
| Active Comparator: mTHS then NRT<br>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<br>* Single use of Tobacco Heating System 2.2 Menthol (mTHS)<br>Other: NRT<br>* Single administration of 2 mg gum (Nicorette® 2mg)<br>|
| Active Comparator: NRT then mTHS<br>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<br>* Single use of Tobacco Heating System 2.2 Menthol (mTHS)<br>Other: NRT<br>* Single administration of 2 mg gum (Nicorette® 2mg)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Nicotine absorption, Candidate modified risk tobacco product, Cigarette, Nicotine replacement therapy, Nicotine gum