Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study

Not Applicable

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
smoking conventional cigarettes (CC)	Conventional cigarettes (CC)	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
smoking conventional cigarettes (CC)	THS 2.1	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
using the Tobacco Heating System 2.1 (THS 2.1)	Conventional cigarettes (CC)	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
using the Tobacco Heating System 2.1 (THS 2.1)	THS 2.1	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

Primary Outcome Measures

Name	Time	Method
Nicotine Cmax	Single use (1 day)	Maximum plasma concentration (Cmax)
Nicotine AUC	Single use (1 day)	Nicotine plasma concentration, area under the curve (AUCt)

Secondary Outcome Measures

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