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 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.

Official Title
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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

Conditions
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Smoking

Intervention / Treatment
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* Other: THS 2.2
* Other: CC
* Other: NRT Gum


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 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.

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: 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 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 cigarette (CC)<br>|
| Active Comparator: THS 2.2 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 THS 2.2) Day 2 = wash-out Day 3 = 2nd intervention (single administration of NRT gum [Nicorette® 2mg]). | Other: THS 2.2<br>* Single use of the Tobacco Heating System 2.2 (THS 2.2)<br>Other: NRT Gum<br>* Single administration of the nicotine replacement therapy (NRT) 2 mg gum (Nicorette® 2mg)<br>|
| Active Comparator: NRT 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 NRT gum [Nicorette® 2mg]) 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: NRT Gum<br>* Single administration of the nicotine replacement therapy (NRT) 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 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 | 

 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, Cigarettes, Nicotine Replacement Therapy gum (NRT gum)