A 26-week Extension of the ZRHR-ERS-09-US Study Evaluating Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2

Study Overview
=================
Brief Summary
-----------------
The objective of the ZRHR-ERS-09-EXT-US study is to further assess the effect of the Tobacco Heating System 2.2 (THS 2.2), a candidate Modified Risk Tobacco Product, compared to conventional cigarettes (CC) on the components of the smokers' health profile for a prolonged period of 26 weeks, providing additional information to the results of the original study ZRHR-ERS-09-US of 26-week exposure (NCT02396381). In total, the ZRHR-ERS-09-EXT-US study will extend the exposure period to 52 weeks.

Detailed Description
-----------------
The ZRHR-ERS-09-EXT-US study is a 26-week extension of the original study ZRHR-ERS-09-US. The subjects in the Full Analysis Set - As Exposed (FAS-EX) included subjects for combined analyses from the original six month study (ZRHR-ERS-09-US ) who did not enter the extension study (ZRHR-ERS-09-EXT-US). This study was conducted as a separate investigation, as a follow-up of the randomized exposure period of the original study, extending the exposure from Week 26 (Visit 10 [V10]) to Week 52 (Visit 16 [V16]), and using the same sites. Subjects continued to use the product they were randomized to in the original study ZRHR-ERS-09-US (THS 2.2 arm or CC arm).

Official Title
-----------------
A 26-week Extension Study to Determine the Biological and Functional Changes in Healthy Smokers Who Switched From Conventional Cigarettes (CC) to Tobacco Heating System 2.2 (THS 2.2) Compared to Those Who Continued to Smoke CC in the ZRHR-ERS-09-US Study

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject completed V10 of the original study (ZRHR-ERS-09-US). The subject is willing to comply to study procedures and to continue to use the product he/she was allocated to during the original study (THS 2.2 or CC) for an additional 26 weeks at V10. Subject has given written informed consent to enter the 26-week extension study at V10. Exclusion Criteria: Clinically relevant medical conditions that in the opinion of the investigators would jeopardize the safety of the participant. As per judgment of the PI(s) or designee(s), the subject cannot participate in the study for any reason (e.g. medical, psychiatric and/or social reason). Subject has made an attempt to quit using tobacco-containing products (e.g. CC and THS 2.2) during the original study. 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. The subject's own preferred brands of CC (no brand restriction) continue to be used as the reference product.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of High Density Lipoprotein C (HDL-C). | Concentrations (mg/dL) measured in serum. Mean values are provided as descriptive statistics. | 52 weeks | 
| Levels of White Blood Cells (WBC). | Total count in blood (GI/L). Mean values are provided as descriptive statistics. | 52 weeks | 
| Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1). | FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics. | 52 weeks | 
| Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1). | Concentrations (ng/mL) measured in serum. Geometric Mean values are provided as descriptive statistics. | 52 weeks | 
| Concentrations of 11-dehydrothromboxane B2 (11-DTXB2). | Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics. | 52 weeks | 
| Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α). | Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics. | 52 weeks | 
| Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). | Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics. | 52 weeks | 
| Levels of Carboxyhemoglobin (COHb). | Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric Mean values are provided as descriptive statistics. | 52 weeks | 

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