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

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 compared to the PK profiles from a single use of a conventional cigarette (CC) and from a single use of 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 (THS 2.2) Following Single Use in Smoking, Healthy Subjects Compared to Conventional Cigarettes and Nicotine Nasal Spray.

Conditions
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Smoking

Intervention / Treatment
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* Other: THS 2.2
* Other: CC
* Other: NNS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is Caucasian Smoking, healthy subject as judged by the Investigator. Subject has smoked at least 10 commercially available non menthol CCs 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 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: 21 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: THS 2.2 then CC<br>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<br>* Single use of the Tobacco Heating System 2.2 (THS 2.2)<br>Other: CC<br>* Single use of subject's own conventional cigarette (CC)<br>|
| Active Comparator: CC then THS 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 CC) Day 2 = wash-out Day 3 = 2nd intervention (single product use of THS 2.2). | Other: THS 2.2<br>* Single use of the Tobacco Heating System 2.2 (THS 2.2)<br>Other: CC<br>* Single use of subject's own conventional cigarette (CC)<br>|
| Active Comparator: THS 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 THS 2.2) Day 2 = wash-out Day 3 = 2nd intervention (single administration of NNS) | Other: THS 2.2<br>* Single use of the Tobacco Heating System 2.2 (THS 2.2)<br>Other: NNS<br>* Single administration of 1 mg of nicotine<br>|
| Active Comparator: NNS then THS 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 THS 2.2). | Other: THS 2.2<br>* Single use of the Tobacco Heating System 2.2 (THS 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 THS 2.2, CC 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 | 
| 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 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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Smoking, Nicotine absorption, Modified risk tobacco product, Conventional cigarette, Nicotine replacement therapy, Nicotine nasal spray