Nicotine Pharmacokinetics of THS Single Use of a Regular or a Menthol Stick Compared to CIG

Study Overview
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Brief Summary
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The purpose of this study is to describe the nicotine pharmacokinetic (PK) profile during and after single use of THS (Induction heating technology, with either a regular or menthol stick) compared to singular CIG smoking in healthy adult subjects. In addition, pharmacodynamic effects (subjective effects) will be evaluated to provide further insights on product acceptance and likelihood to use the THS again. Safety will be assessed throughout the study.

Official Title
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A Single-center, Randomized, Controlled, Open-label Study in Smoking Healthy Subjects to Investigate the Nicotine Pharmacokinetic Profiles Following Single Use of Tobacco Heating System (THS) With a Regular or a Menthol Stick, Compared to Smoking of a Single Combustible Cigarette (CIG)

Conditions
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Smoking, Tobacco

Intervention / Treatment
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* Other: P1R stick
* Other: P1M stick
* Other: CIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed the 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 in total). Subject has continuously smoked on average ≥10 commercially available regular CIG/day over the last 4 weeks. 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). Subject does not plan to quit smoking within the next three months. Exclusion Criteria: As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical (e.g., psychological, social reason). Subject is legally incompetent, or physically or mentally incapable of giving consent (e.g., in emergency situations, under guardianship, prisoners). 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.) or the subject has a confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment) 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, or current asthma condition or COPD condition, and/or clinically significant findings. Subject has donated blood or received whole blood or blood products within 3 months. BMI < 18.5 kg/m2 or ≥ 32.0 kg/m2. Positive serology test for HIV 1/2, HBV, or HCV. Subject has a positive alcohol breath test and/or has a history of alcohol disorder that could interfere with their participation in the study. The subject has a positive urine drug test. Subject or one of their family members is a current or former employee of the tobacco or e-cigarette industry. Subject or one of their family members is an employee of the investigational site or of any other parties involved in the study. Subject has participated in another clinical study within 3 months. Subject has been previously screened or enrolled in this study. Subject is pregnant (does not have negative pregnancy tests at Screening and at Baseline) or is breastfeeding. For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Product Sequence 1<br>After at least 23 hours of abstinence from any Tobacco or Nicotine Product (TNP) on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 2<br>After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 3<br>After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 4<br>After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 5<br>After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 6<br>After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R | Other: P1R stick<br>* Regular flavor tobacco stick<br>Other: P1M stick<br>* Mentholated flavor tobacco stick<br>Other: CIG<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration [Cmax] | To measure Cmax from the single use of THS with either a regular or a menthol stick or of a single cigarette. | Measured from start of product use to 24 hours | 
| Time to the maximum concentration [Tmax] | To measure Tmax from the single use of THS with either a regular or a menthol stick or of a single cigarette. | Measured from start of product use to 24 hours | 
| Area under the curve of nicotine plasma concentration-time computed from T0 to T=24 hours [AUC0-24h] | To measure AUC0-24h from the single use of THS with either a regular or a menthol stick or of a single cigarette. | Measured from start of product use to 24 hours | 
| Area under the curve of nicotine plasma concentration-time computed from T0 to the subject-specific time of maximum nicotine concentration [AUC0-t'] | To measure AUC0-t' from the single use of THS with either a regular or a menthol stick or of a single cigarette. | Measured from start of product use to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine, Nicotine-containing products, Heated tobacco, Smoking, Tobacco, Tobacco Heating System, Pharmacokinetics