Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting

Study Overview
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Brief Summary
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Evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS), a candidate Modified Risk Tobacco Product, for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs).

Detailed Description
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The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS) for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful 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
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A Randomized, Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Apparently Healthy Smokers Switching to the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) or Observing Smoking Abstinence, Compared to Continuing to Use Menthol Conventional Cigarettes, for 5 Days in Confinement and Prolonged by 86 Days in an Ambulatory Setting

Conditions
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Smoking

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoking, apparently 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 within the next 6 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
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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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 86 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 86 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 86 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 86 days in an ambulatory setting<br>|
| Sham Comparator: Smoking abstinence (SA)<br>Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting | Other: Smoking Abstinence (SA)<br>* SA for 5 days in confinement prolonged by 86 days in an ambulatory setting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Monohydroxybutenylmercapturic Acid (MHBMA) | Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics. | 5 days | 
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics. | 5 days | 
| Concentration of S-phenylmercapturic Acid (S-PMA) | Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics. | 5 days | 
| Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL) | Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics. | 90 days | 
| Levels of Carboxyhemoglobin (COHb) | Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics. | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Candidate modified risk tobacco product, Menthol conventional cigarettes, Reduced exposure, HPHCs, Ambulatory