Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to demonstrate clinical, biological and functional health changes in smokers switching to the candidate modified risk tobacco product: Tobacco Heating System 2.2 (THS 2.2) as compared to smokers continuing smoking their conventional cigarettes (CC) over a 26-week period. To characterize the study as successful, at least 5 clinical risk endpoints should move in the direction of smoking cessation and these results would be statistically significant. The main analysis will be defined a priori (using the Hailperin-Ruger approach) and will be made between THS 2.2 use and CC use as per actual product used and product use categories.

Detailed Description
-----------------
The clinical, biological and functional endpoints to be measured in this study (smoker's health profile) may characterize the modification of risk of smoking-related diseases. Clinical risk endpoint to be assessed are selected based on a) their association to smoking-related diseases b) their association to smoking status, c) their reversibility upon smoking cessation, and d) their suitability to be measured with valid and robust methods in clinical studies. The biological markers, functional markers and biomarkers of exposure (BoExp) with the strongest scientific evidence will constitute the 'smoker's health profile' and will be measured as the primary objective of the study. Additional endpoints involved in the mechanistic of smoking-related diseases will be studied to provide additional scientific evidence to strengthen the primary objective. The study will provide a perspective of product usage in a real world setting where smoking CC in addition to THS 2.2 may be expected.

Official Title
-----------------
A Randomized, Controlled, 2-arm Parallel Group, Multi-center Study, to Evaluate Biological and Functional Changes in Healthy Smokers Switching to Tobacco Heating System 2.2 (THS 2.2) Compared to Continuing Smoking Conventional Cigarettes for 26 Weeks in an Ambulatory Setting

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Current healthy smoker as judged by the Principal Investigator(s) or designee(s) Minimum age: 30 years old Have smoked for the last 10 years Have smoked more than 10 non menthol CC/day on average (no brand restriction) over the past year Exclusion Criteria: Clinically relevant medical conditions that in the opinion of the investigators would jeopardize the safety of the participant. Subject who has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry Subject with asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values) Subject who took or is taking concomitant medication which may have an impact on the smoker's heath profile Female subject is pregnant or breast feeding. Female subject who does not agree to use an acceptable method of effective contraception.

Ages Eligible for Study
-----------------
Minimum Age: 30 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<br>Ad libitum use of THS 2.2 | Other: THS 2.2<br>* Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks<br>|
| Active Comparator: CC<br>Ad libitum use of CC | Other: CC<br>* Ad libitum use of CC in an ambulatory setting for 26 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of High Density Lipoprotein C (HDL-C). | Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Levels of White Blood Cells (WBC). | Concentrations measured in blood. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1). | FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1). | Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Concentrations of 11-dehydrothromboxane B2 (11-DTXB2). | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α). | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. | 26 Weeks | 
| Percent Change From Baseline of Carboxyhemoglobin (COHb) | Carboxyhemoglobin (COHb) is assayed from whole blood. Geometric Least Squares means are provided as descriptive statistics. Expressed as % of saturation of hemoglobin. | 26 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Candidate modified risk tobacco product, Conventional cigarette, Exposure response, Smoking, Tobacco Heating System