Reduced exposure to HPHC in smokers switching from cigarettes to THS
Research type
Research Study
Full title
A randomized, controlled, open-label, 4 parallel arms study to demonstrate reductions in exposure to selected harmful and potentially harmful constituents (HPHC) of cigarette (CIG) smoke in healthy smokers switching to different versions of Tobacco Heating System (THS) compared to continuing CIG smoking, for 5 days in confinement
IRAS ID
318514
Contact name
Christelle Haziza
Contact email
Sponsor organisation
Philip Morris Products S.A.
Duration of Study in the UK
0 years, 3 months, 24 days
Research summary
Research Summary
This clinical study aims to demonstrate the reduction of BoExp(Biomaker of exposure) to selected HPHC(Harmful and potentially harmful constituents) in smokers switching from CIG to each of the THS(Tobacco Heating System) variants with different heating technology (Blade device, or Induction Mono device, or Induction Mid device, respectively), compared to smokers who continue to smoke CIG. A reduction of exposure to HPHC derived from CIG smoke is expected to reduce the health risk of CIG consumption if switching completely to THS.
This is an ad libitum use/smoking study. During confinement, in general, THS use and CIG consumption (according to randomization) will be allowed between 06:30 AM and 11:00 PM.
During the confinement period, adherence to product arm allocation (exclusive use of THS Blade device, or Induction Mono device, or Induction Mid device, or CIG) will be ensured by strict distribution of the devices, and of each stick/CIG upon demand of the subject to the site staffSummary of Results
General information about the research:
• Study Title:
Reduced Exposure to Harmful and Potentially Harmful Constituents (HPHC) in Smokers Switching From Cigarettes to Different Versions of the Tobacco Heating System (THS)• Who carried out the research?
This research was sponsored and funded by Philip Morris Products S.A.• What public involvement there was in the study?
Ninety-one healthy, currently smoking, adults participated in this study.• Where and when the study took place?
The study was conducted at a clinical trial facility managed by a contract research organization in Belfast, Northern Ireland, from November 16th 2022 to February 6th 2023.• Why was the research needed?
The research was needed to understand the reductions in exposure to selected HPHC of Cigarette smoke in healthy smokers, who switched exclusively to an electronic nicotine delivery system for 5 days.• What were the main questions studied?
The study measured the reductions in exposure to selected HPHC of cigarette smoke in healthy smokers switching for 5 days from Cigarettes to the THS devices with different heating systems (blade or induction), that is, Blade, Induction Mono, or Induction Mid, compared to continuing Cigarette smoking.
Who participated in the study?
Ninety-one healthy male or female adults, aged between 21 and 65 years, participated in this study. All participants were currently smoking. The participants did not plan to quit using tobacco and/or nicotine products within the next 3 months and had smoked continuously for at least the last 3 years prior to joining the study.
Each participant was given full and adequate oral and written information about the nature, purpose, possible risks, and benefits of the study.
All participants received information on the risks of smoking, smoking cessation advice and a briefing on the Tobacco Heating System, for example, that its use is not risk-free.
Once each participant had received all the necessary information, and if they agreed to participate, this was documented in an Informed Consent Form with the date, time, and signature of both the participant and the study doctor.
Participants were informed that they were free to withdraw from the study at any time.What treatments or interventions did the participants take/receive?
Eighty participants were randomly assigned to one of four study arms: THS Blade device, THS Induction Mono device, THS Induction Mid device, or Cigarette, for five days in a confinement setting.
Participants assigned to one of the THS arms or the Cigarette arm could use their assigned product, as often as they wished, from 6:30 AM to 11:00 PM during the five-day confinement period.
Urine was collected from each participant for analysis, for each 24 hours, from Day -1 (the start of the confinement period) to Day 5 (until discharge at the morning of Day 6).
Participants were also asked to evaluate their experience of using their assigned products, using a product experience questionnaire.
The questionnaire assessed the perceived effects experienced by Cigarette smokers switching to the THS Blade device, THS Induction Mono device, or THS Induction Mid device compared to the experience of subjects continuing Cigarette smoking.
The product experience questionnaire measured the degree to which participants experienced five different effects (Product Satisfaction, Psychological Rewards, Aversion, Enjoyment of Respiratory Tract Sensations (single-item assessment); Craving Relief), rated on a 7 point scale from 1 = “not at all” to 7 = “extremely.”What medical problems (adverse reactions) did the participants have?
Overall, 24 adverse reactions occurred in 17 participants, all of them being mild or moderate in severity.
The proportion of subjects experiencing adverse reactions was mostly comparable across the different devices. No adverse reactions were observed in the Cigarette arm. None of the adverse reactions led to a discontinuation.
Vital signs results, EGG parameters, and spirometry results were comparable between the study arms with no notable trends. Safety laboratory data (hematology, clinical chemistry, and urinanalysis) were comparable between the study arms. Whilst a small number of measurements were deemed as abnormal, none were considered clinically significant.What happened during the study?
A presentation of THS (without product use) was made to the participants during the Screening visit. All participants received information on the risks of smoking, smoking cessation advice, and a briefing that the use of THS is not risk-free. Eligible participants, fulfilling all criteria for participation, returned to the investigational site for confirmation of eligibility at the Admission visit (Day -2).
On Day -2 (Admission), after eligibility criteria had been verified, subjects had a product test of the THS Blade device and Induction Mono device (with use of up to three THS tobacco sticks per device). All eligible participants were then enrolled and participants willing to continue their participation in the study started their confinement period of seven days.
On Day -1, participants were randomly assigned to one of four arms: THS Blade device, THS Induction Mono device, THS Induction Mid device, or Cigarette.
Participants were informed about their randomization arm by the study site staff on Day 1 prior to the start of product use.
The Exposure period in confinement began on Day 1 and consisted of 5 days of at will use of the assigned product in the THS and Cigarette arms. Use of any tobacco/nicotine containing product other than the assigned product was not allowed.
Daily 24-hour urine was collected from Day -1 to Day 5 for HPHC analysis. On Day 1, use of THS or Cigarette smoking in the respective arms was not supposed to start before the end of 24-hour urine collection of Day -1. The 24-hour urine collection period for Day 5 ended in the morning of Day 6 prior to Discharge.
On Day -1 and on Days 1 to 5, participants completed questionnaires to assess the perceived effects experienced after switching to THS, compared to the experience of participants who continued Cigarette smoking.
During the confinement period, adherence to investigational product arm allocation (exclusive use of the assigned THS devices with designated sticks, or Cigarette smoking, respectively) was ensured by strict distribution of the devices, and of each stick/cigarette upon demand of the subject to the study site staff.
Any participant who wanted to attempt to quit using any tobacco or nicotine containing product at any time during the study (that is, to quit THS use or Cigarette smoking) was encouraged to do so and was to be referred to appropriate medical services. This decision would not affect the participant’s financial compensation, and the participant was to be considered as remaining in the study.
The Exposure period to the assigned investigational product (THS or Cigarette) ended at 11:00 PM on Day 5, followed by Discharge on Day 6 after completion of all study procedures. Participants were allowed to smoke Cigarettes or use other tobacco or nicotine-containing products, at their discretion, only after discharge from the study.
After discharge at Day 6 or from the day of an early termination, subjects entered a 3-day Safety follow-up period during which any adverse reactions reported by the participants were collected. The follow-up of adverse reactions ongoing at discharge was conducted by the investigational site.What were the results of the study?
The HPHC of Cigarette smoke were examined by measuring their degradation products in participant’s urine. These degradation products are called Biomarkers of Exposure.
The results of this study demonstrated that on Day 5 in subjects who switched to one of the THS devices, levels of Biomarkers of Exposure to the HPHC of Cigarette smoke were significantly lower compared to those who continued smoking Cigarettes.
The magnitude of reduction in the levels of Biomarkers of Exposure were comparable between each THS device (THS Blade, THS Induction Mid, and THS Induction Mono).
Furthermore, no additional safety concerns were associated with THS use compared to Cigarette smoking.How has this study helped patients and researchers?
The participants in this study were healthy, current Cigarette smokers. All participants were informed about the health risks associated with smoking and were given smoking cessation advice. Participants in this clinical study benefited from repeated and detailed general health check-ups.
This clinical study may help doctors and scientists learn about electronic nicotine delivery systems, for example the THS devices examined in this study.
The exposure period in confinement provided information on the exposure reductions achievable for HPHC in a well-controlled environment with full control over daily THS use and/or Cigarette consumption.Details of any further research planned
This study is part of an ongoing program of research supporting the scientific substantiation of the Tobacco Heating System.Where can I learn more about this study?
More details about this study, including the study results and a copy of the study protocol, can be found on the clinicaltrials.gov website at this address:
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HSC REC A
REC reference
22/NI/0138
Date of REC Opinion
3 Oct 2022
REC opinion
Favourable Opinion