Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study

Study Overview
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Brief Summary
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The main goal of this exploratory study is to evaluate the pharmacokinetic profile of nicotine for the candidate modified risk tobacco product THS 2.1 and for conventional cigarettes (CC).

Detailed Description
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This 2-period 2-sequence cross-over clinical study intends to explore the profile of nicotine uptake (rate and extent of nicotine absorbed and associated variability) in healthy smokers switching from (CC) to THS 2.1 (single or ad libitum use) compared to smokers continuing to use CC, as a comparator. This study will serve to optimize blood sampling schedules and sample size estimation for further studies. This study will also provide preliminary information on the relationship between nicotine absorption and urge to smoke/withdrawal symptoms when using THS 2.1 as compared to CC, as well as the safety profile, which is related to the use of THS 2.1. After screening, enrolled subjects will be admitted to the clinic for 8 days. This study duration includes 2 consecutive periods. Each period consists of 1 day for single use of the product preceded by a 24-hour nicotine deprivation, and 1 day for ad libitum product use. After leaving the clinic, the subjects will be followed up for safety over a period of 7 days. This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.

Official Title
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A Single-center, Open-label, Randomized, Controlled, Crossover Study to Explore the Nicotine Pharmacokinetic Profile and Safety of Tobacco Heating System (THS) 2.1 Compared to Conventional Cigarettes Following Single and ad Libitum Use in Smoking, But Otherwise Healthy Subjects.

Conditions
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Smoking

Intervention / Treatment
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* Other: Conventional cigarettes (CC)
* Other: THS 2.1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed an informed consent form before commencement of study procedures Healthy Caucasian aged between 23 to 65 years Subject is current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months Exclusion Criteria: As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason) The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results The subject has participated in a clinical study within 3 months prior to the Screening Visit Pregnant or lactating woman, and for woman of childbearing potential, absence / refusal to use an acceptable method of effective contraception

Ages Eligible for Study
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Minimum Age: 23 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: smoking conventional cigarettes (CC)<br>After a 1-day nicotine deprivation, subjects are smoking one single cigarette (usual own brand) on one day and then smoking ad libitum on the subsequent day | Other: Conventional cigarettes (CC)<br>* Subjects are randomized in a 1:1 fashion to be assigned to one of the 2 sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC.<br>Other: THS 2.1<br>* Subjects are randomized in a 1:1 fashion to be assigned in one of the sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC<br>|
| Experimental: using the Tobacco Heating System 2.1 (THS 2.1)<br>After a 1-day nicotine deprivation, subjects are puffing one single tobacco stick using the THS 2.1 on one day and then puffing ad libitum on the subsequent day | Other: Conventional cigarettes (CC)<br>* Subjects are randomized in a 1:1 fashion to be assigned to one of the 2 sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC.<br>Other: THS 2.1<br>* Subjects are randomized in a 1:1 fashion to be assigned in one of the sequences, either A) CC and then THS 2.1, or B) THS 2.1 and then CC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Cmax | Maximum plasma concentration (Cmax) | Single use (1 day) | 
| Nicotine AUC | Nicotine plasma concentration, area under the curve (AUCt) | Single use (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine concentrations | Time course of plasma nicotine concentration | Single use (1 day); multiple use (1 day) | 
| Questionnaire of smoking urges (brief version) (QSU-brief) | QSU-brief measuring subjective effects of smoking | single use (1 day); multiple use (1 day) | 
| Safety monitoring | Monitoring of adverse events, based on clinical and laboratory evaluation | 7 days + 7 days follow-up | 
| Nicotine tmax | Time to maximal nicotine concentration in plasma | Single use (1 day) | 
| Cough Visual Analog Scale | Visual Analog Scale on cough | 7 days | 
| Modified Cigarette Evaluation Questionnaire (MCEQ) | MCEQ measuring effects of smoking | single use (1 day); multiple use (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Modified risk tobacco product (MRTP), Smoking, Nicotine profile