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 the study is to evaluate the pharmacokinetic (PK) profiles (rate and amount of nicotine absorbed) after a single use of the THS 2.2 Menthol (mTHS 2.2) compared to a single use of the menthol conventional cigarette (mCC) and nicotine nasal spray (NNS).

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 Nasal Spray

Conditions
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Smoking

Intervention / Treatment
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* Other: mTHS 2.2
* Other: mCC
* Other: NNS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is aged from 22 to 65 years (inclusive). Smoking, healthy subject as judged by the Investigator. Subject smoked at least 10 commercially available menthol CCs per day (with brand restrictions) over the last 4 weeks. Subject has smoked for at least the last 3 consecutive years. 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.

Ages Eligible for Study
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Minimum Age: 22 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 2.2 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 2.2) Day 2 = wash-out Day 3 = 2nd intervention (single product use of mCC). | Other: mTHS 2.2<br>* Single use of mTHS 2.2<br>Other: mCC<br>* Single use of subject's own mCC<br>|
| Active Comparator: mCC then mTHS 2.2<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 2.2). | Other: mTHS 2.2<br>* Single use of mTHS 2.2<br>Other: mCC<br>* Single use of subject's own mCC<br>|
| Active Comparator: mTHS 2.2 then NNS<br>Each subject will follow the below study design: Day 0 = Wash-out (1 day) Day 1 = 1st intervention (single product use of mTHS 2.2) Day 2 = wash-out Day 3 = 2nd intervention (single administration of NNS) | Other: mTHS 2.2<br>* Single use of mTHS 2.2<br>Other: NNS<br>* Single administration of 1 mg of nicotine<br>|
| Active Comparator: NNS then mTHS 2.2<br>Each subject will follow the below study design: Day 0 = Wash-out (1 day) Day 1 = 1st intervention (single administration of NNS) Day 2 = wash-out Day 3 = 2nd intervention (single product use of mTHS 2.2). | Other: mTHS 2.2<br>* Single use of mTHS 2.2<br>Other: NNS<br>* Single administration of 1 mg of nicotine<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 2.2, mCC and NNS | 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 (geometric LS) means are provided. | 3 days | 
| Area Under the Plasma Nicotine Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of mTHS 2.2, mCC and NNS | 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. | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Candidate modified risk tobacco product, Conventional cigarette, Nicotine replacement therapy: nasal spray, Smoking, Nicotine absorption