Reduced Exposure Study Using the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting.

Study Overview
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Brief Summary
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The overall goal of the study is to demonstrate reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) identified in cigarettes and to obtain safety information in healthy adult smokers switching to the Carbon Heated Tobacco Product 1.2 (CHTP 1.2) as compared to subjects continuing smoking cigarettes (CC) in a confinement setting for 5 days (exclusive use) followed by an ambulatory setting of 85 days.

Official Title
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A Randomized, Controlled, Open-label, 2-arm Parallel Group, Single Center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Healthy Smokers Switching to the Carbon Heated Tobacco Product 1.2 (CHTP 1.2), Compared to Continuing to Use Combustible Cigarettes, for 5 Days in Confinement Followed by 85 Days in an Ambulatory Setting.

Conditions
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Smoking

Intervention / Treatment
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* Other: CHTP 1.2
* Other: CC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is aged ≥ 28 years. Subject is Caucasian. Subject is healthy, as judged by the Investigator. Subject has smoked at least 10 commercially available non-menthol CCs per day (no brand restrictions) at least for the last 6 weeks prior to the screening visit and admission. Subject has smoked at least for the last 10 years. Subject does not plan to quit smoking in 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). 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 1A2 (CYP1A2) or cytochrome P450 2A6 (CYP2A6) activity. Female subject is pregnant or breast feeding. Female subject does not agree to use an acceptable method of effective contraception.

Ages Eligible for Study
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Minimum Age: 28 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: CHTP 1.2<br>Ad libitum use of the CHTP 1.2 | Other: CHTP 1.2<br>* Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.<br>|
| Active Comparator: CC<br>Ad libitum use of subject's own preferred non-menthol brand of CC | Other: CC<br>* Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. | 5 days | 
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. | 5 days | 
| Concentration of S-phenylmercapturic Acid (S-PMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. | 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 (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. | 5 days | 
| Concentrations 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 and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 90 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Cigarettes, Reduced exposure, Confinement, Ambulatory, Carbon Heated Tobacco Product