Reduced HPHC Exposure in Cigarette Smokers Switching to P4M3 Gen. 2.0 Compared to Continuing Smoking, or Smoking Abstinence

Study Overview
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Brief Summary
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To demonstrate the reduction of Biomarkers of Exposure (BoExp) to selected harmful and potentially harmful constituents (HPHC) in smokers switching from cigarette (CIG) to P4M3, an Electronic Nicotine Delivery System (ENDS), compared to continuing cigarette smoking for 5 days.

Detailed Description
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This clinical study aims to demonstrate the reduction of BoExp to selected HPHC in smokers switching from CIG to two flavor variants of P4M3 as compared to smokers continuing smoking CIG, or to smoking abstinence (SA). A reduction of exposure to HPHC from CIG smoke is expected to diminish the health risk of nicotine consumption if switching completely to ENDS. The data collected in this study in confinement will provide information on exposure reductions achievable in a well-controlled environment with full control on daily P4M3/CIG consumption and compared to SA.

Official Title
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A Randomized, Controlled, Open-label, 4-arm Parallel Group Study to Demonstrate Reductions in Exposure to Selected Harmful and Potentially Harmful Constituents (HPHC) in Healthy Smokers Switching to 2 Variants of P4M3 Gen 2.0, an Electronic Nicotine Delivery System (ENDS), Compared to Continuing Smoking Cigarettes, or Abstaining From Smoking, for 5 Days in a Confinement Setting

Conditions
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Nicotine, Vaping, Nicotine Vaping

Intervention / Treatment
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* Other: P4M3 CA35
* Other: P4M3 CM35
* Other: CIG
* Other: Smoking Abstinence


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Subject has signed the Informed Consent Form (ICF) and is able to understand the information provided in the ICF. Subject has been a smoker for ≥3 years prior to the screening visit (smoking cessation attempts during this period, if any, did not last >6 months). Subject has continuously smoked on average ≥10 commercially available mentholated or non-mentholated CIGs per day over the last 4 weeks prior to screening and admission. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL). Subject is healthy as judged by the Investigator based on available assessments from the screening period (e.g., safety laboratory, spirometry, vital signs, physical examination, ECG, and medical history). Main Exclusion Criteria: Subject has a clinically relevant disease which requires medication (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or any other medical condition (including safety laboratory), which as per the judgment of the Investigator would jeopardize the safety of the subject. Subject experienced within 30 days prior to screening/admission a body temperature >37.5°C or an acute illness (e.g., upper respiratory-tract infection, viral infection, etc.) As per the Investigator's judgment, the subject has medical conditions which do or will require a medical intervention (e.g., start of treatment, surgery, hospitalization) during the study participation, which may interfere with the study participation and/or study results. Subject has relevant history of a current asthma condition or chronic obstructive pulmonary disease (COPD) condition, and/or clinically significant spirometry findings at Screening or Baseline Subject has donated blood or received whole blood or blood products within 3 months prior to screening. BMI <18.5 kg/m2 or ≥32.0 kg/m2.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: P4M3 CA35<br>Ad libitum use of P4M3 using CA35 Cartridges | Other: P4M3 CA35<br>* Ad libitum use of P4M3 with CA35 cartridges<br>* Other names: P4M3 Classic Auburn 3.5% nicotine (CA35);|
| Active Comparator: P4M3 CM35<br>Ad libitum use of P4M3 using CM35 Cartridges | Other: P4M3 CM35<br>* Ad libitum use of P4M3 with CM35 cartridges<br>* Other names: P4M3 Classic Menthol 3.5% nicotine (CM35);|
| Active Comparator: Cigarette<br>Ad libitum use of subject's own preferred CIG brand | Other: CIG<br>* Ad libitum use of subject's own preferred brand of cigarettes<br>* Other names: Cigarette;|
| Active Comparator: Smoking Abstinence<br>Smoking abstinence | Other: Smoking Abstinence<br>* Abstention from cigarette smoking<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-HPMA | To measure change in 3-hydroxypropyl mercapturic acid (3-HPMA), which is a biomarker of exposure to Acrolein. | From baseline to 5 days | 
| 2-CyEMA | To measure change in 2-cyanoethyl mercapturic acid (2-CyEMA), which is a biomarker of exposure to Acrylonitrile. | From baseline to 5 days | 
| Total NNAL | To measure change in Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL), which is a biomarker of exposure to 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK). | From baseline to 5 days | 
| COHb | To measure change in carboxyhemoglobin (COHb), which is a biomarker of exposure to Carbon monoxide (CO). | From baseline to 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaping, Nicotine, Smoking, Cigarette, E-Cigarette, Electronic Nicotine Delivery System