Nicotine Pharmacokinetic Profile of the CHTP 1.1 M

Study Overview
=================
Brief Summary
-----------------
The primary objective of this clinical study is to evaluate the pharmacokinetic (PK) profile of nicotine (rate and amount of nicotine absorbed) after single use of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M), a potential Modified Risk Tobacco Product, compared to menthol cigarettes (mCC) in healthy smokers.

Official Title
-----------------
A Single-center, Open-label, Randomized, Controlled, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M) Following Single Use in Smoking, Healthy Subjects Compared to Menthol Conventional Cigarettes

Conditions
-----------------
Smoking

Intervention / Treatment
-----------------
* Other: CHTP 1.1 M
* Other: mCC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is Japanese. Subject is at a minimum 23 years of age. Smoking, healthy subject as judged by the Investigator. Subject has smoked for at least the last 3 years Subject smoked at least 10 commercially available mCCs per day over the last 4 weeks. 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
-----------------
Minimum Age: 23 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: CHTP 1.1 M then mCC<br>Each subject will follow the below study design: Day -1 = Wash-out (1 day) Day 1 = 1st intervention (single product use of CHTP 1.1 M) Day 2 = Wash-out Day 3 = 2nd intervention (single product use of mCC). | Other: CHTP 1.1 M<br>* Single use of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M)<br>Other: mCC<br>* Single use of subject's own menthol conventional cigarette (mCC)<br>|
| Active Comparator: mCC then CHTP 1.1 M<br>Each subject will follow the below study design: Day -1 = 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 CHTP 1.1 M). | Other: CHTP 1.1 M<br>* Single use of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M)<br>Other: mCC<br>* Single use of subject's own menthol conventional cigarette (mCC)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of Nicotine Following Single Use of CHTP 1.1 M and mCC | 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 (LS) means are provided. | Day 3: 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 Versus Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of CHTP 1.1 M and mCC | 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. | Day 3: 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
smoking, nicotine absorption, potential modified risk tobacco product, cigarette, Carbon Heated Tobacco Product