Exploratory THS 2.1 Nicotine Pharmacokinetics and Safety Study

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.

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).

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: Conventional cigarettes (CC); Other: THS 2.1

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 AD6
    • Celerion, 22-24 Lisburn Road

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: smoking 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	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.; Other: 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
EXPERIMENTAL: using the Tobacco Heating System 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	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.; Other: 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Adrian J Stewart, MD, Celerion, Belfast, Northern Ireland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (ESTIMATE): January 31, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Smoking; Modified risk tobacco product (MRTP); Nicotine profile
• Other Study ID Numbers: ZRHX-PK-02