Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study

Smoking Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780688
• Other study ID #: ZRHX-PK-02
• Status: Completed
• Phase: N/A
• Start date: May 2012
• Est. completion date: December 2012

Study information

• Verified date: November 2019
• Source: Philip Morris Products S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 23 Years to 65 Years

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

Related Conditions & MeSH terms

• Smoking

Intervention

Other:
• Conventional cigarettes (CC)
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.
• THS 2.1
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

Locations

Country	Name	City	State
United Kingdom	Celerion, 22-24 Lisburn Road	Belfast

Sponsors (1)

Lead Sponsor	Collaborator
Philip Morris Products S.A.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Picavet P, Haziza C, Lama N, Weitkunat R, Lüdicke 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nicotine Cmax	Maximum plasma concentration (Cmax)	Single use (1 day)
Primary	Nicotine AUC	Nicotine plasma concentration, area under the curve (AUCt)	Single use (1 day)
Secondary	Nicotine concentrations	Time course of plasma nicotine concentration	Single use (1 day); multiple use (1 day)
Secondary	Questionnaire of smoking urges (brief version) (QSU-brief)	QSU-brief measuring subjective effects of smoking	single use (1 day); multiple use (1 day)
Secondary	Safety monitoring	Monitoring of adverse events, based on clinical and laboratory evaluation	7 days + 7 days follow-up
Secondary	Nicotine tmax	Time to maximal nicotine concentration in plasma	Single use (1 day)
Secondary	Cough Visual Analog Scale	Visual Analog Scale on cough	7 days
Secondary	Modified Cigarette Evaluation Questionnaire (MCEQ)	MCEQ measuring effects of smoking	single use (1 day); multiple use (1 day)