Reduced Exposure Study in Smokers Using the Tobacco Heating System 2.2 (THS 2.2) for 5 Days in a Confinement Setting

Study Overview
=================
Brief Summary
-----------------
The overall goal of the study is to evaluate if the ad libitum use of the Tobacco Heating System 2.2 (THS 2.2) for 5 consecutive days by adult Japanese healthy smokers affects the levels of biomarkers of exposure for selected harmful and potentially harmful constituents (HPHCs) compared to smoking conventional cigarettes (CC) and smoking abstinence (SA).

Official Title
-----------------
A Controlled, 3-arm Parallel Group Study to Demonstrate Reduction in Exposure to Smoke Constituents in Healthy Smokers Switching to THS 2.2 or to Smoking Abstinence, Compared to Conventional Cigarettes for 5 Days in Confinement

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

Intervention / Treatment
-----------------
* Other: Tobacco Heating System (THS 2.2)
* Other: Smoking abstinence (SA)
* Other: Conventional cigarette (CC)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is Japanese. Smoking, healthy subject as judged by the Investigator. Subject smokes at least 10 commercially available non-menthol CCs per day (no brand restrictions) for the last 4 weeks, based on self reporting. 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). The subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer), which has an impact on CYP1A2 or CYP2A6 activity. For women: Subject is pregnant or is breast feeding. For women: Subject does not agree to use an acceptable method of effective contraception.

Ages Eligible for Study
-----------------
Minimum Age: 23 Years
Maximum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tobacco Heating System (THS 2.2)<br>Ad libitum use of THS 2.2 for 5 days in confinement | Other: Tobacco Heating System (THS 2.2)<br>* THS 2.2 ad libitum for 5 days in confinement<br>|
| Sham Comparator: Smoking abstinence (SA)<br>Abstinence from smoking for 5 days in confinement | Other: Smoking abstinence (SA)<br>* SA for 5 days in confinement<br>|
| Active Comparator: Conventional cigarette (CC)<br>Ad libitum use of Subject's own preferred brand of CC for 5 days in confinement | Other: Conventional cigarette (CC)<br>* Subject's own preferred brand of CC ad libitum for 5 days in confinement<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares LS) means are provided as descriptive statistics. | 5 days | 
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. | 5 days | 
| Concentration of S-phenylmercapturic Acid (S-PMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. | 5 days | 
| Levels of Carboxyhemoglobin (COHb) | % COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics. | 5 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Candidate modified risk tobacco product, Conventional cigarette, Reduced exposure, HPHCs, Confinement