Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting

Study Overview
=================
Brief Summary
-----------------
The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS 2.2) for 5 days in confinement and after 85 days of product use in an ambulatory setting, by Japanese adult healthy smokers results in a reduction in the levels of biomarkers of exposure for selected harmful and potentially harmful smoke constituents (HPHCs) compared to smokers continuing smoking their own preferred brand of menthol conventional cigarette (mCC) and smoking abstinence (SA). Smokers who remained abstinent from SA were used as a benchmark to provide context to the exposure reduction.

Official Title
-----------------
A Randomized, Controlled, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Smokers Switching to THS 2.2 Menthol or Smoking Abstinence Compared to Smoking Menthol Conventional Cigarettes, for 90 Days

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

Intervention / Treatment
-----------------
* Other: THS 2.2 Menthol (mTHS 2.2)
* Other: Smoking Abstinence (SA)
* Other: Menthol Conventional Cigarette (mCC)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is Japanese. Smoking, healthy subject as judged by the Investigator. Subject smokes at least 10 commercially available mCCs 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 cytochrome P450 1 A2 (CYP1A2) or cytochrome P450 2 A6 (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: THS 2.2 Menthol (mTHS 2.2)<br>Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting | Other: THS 2.2 Menthol (mTHS 2.2)<br>* THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting<br>|
| Active Comparator: Smoking abstinence (SA)<br>Abstinence from smoking for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting | Other: Smoking Abstinence (SA)<br>* SA for 5 days in confinement prolonged by 85 days in an ambulatory setting<br>|
| Active Comparator: Menthol Conventional Cigarette (mCC)<br>Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting | Other: Menthol Conventional Cigarette (mCC)<br>* Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting<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 (LS) 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 (LS) 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 | 
| Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL) | Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 90 days | 

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