Clinical trial NCT01780688: Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Keywords: Modified risk tobacco product (MRTP)
Smoking
Nicotine profile
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2013-01-31
Enrollment: 33
Sex: ALL
Minimum age (years): 23
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Nicotine Cmax
timeFrame: Single use (1 day)
measure: Nicotine AUC
timeFrame: Single use (1 day)
Secondary outcomes:
measure: Nicotine concentrations
timeFrame: Single use (1 day); multiple use (1 day)
measure: Questionnaire of smoking urges (brief version) (QSU-brief)
timeFrame: single use (1 day); multiple use (1 day)
measure: Safety monitoring
timeFrame: 7 days + 7 days follow-up
measure: Nicotine tmax
timeFrame: Single use (1 day)
measure: Cough Visual Analog Scale
timeFrame: 7 days
measure: Modified Cigarette Evaluation Questionnaire (MCEQ)
timeFrame: single use (1 day); multiple use (1 day)
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Celerion, 22-24 Lisburn Road
Study officials:
affiliation: Celerion, Belfast, Northern Ireland
name: Adrian J Stewart, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Picavet P, Haziza C, Lama N, Weitkunat R, Ludicke F. Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes. Nicotine Tob Res. 2016 May;18(5):557-63. doi: 10.1093/ntr/ntv220. Epub 2015 Oct 5.