Nicotine PK of THS regular or menthol stick compared to CIG
Research type
Research Study
Full title
A single-center, randomized, controlled, open-label study in smoking healthy subjects to investigate the nicotine pharmacokinetic profiles following single use of Tobacco Heating System (THS) with a regular or a menthol stick, compared to smoking of a single combustible cigarette (CIG)
IRAS ID
323427
Contact name
Christelle Haziza
Contact email
Sponsor organisation
Philip Morris Products S.A.
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 1 months, 10 days
Research summary
Research Summary
The purpose of this study is to describe the nicotine pharmacokinetic (PK) profile during and after single use of Tobacco Heating System (THS; with either a regular or menthol stick) compared to singular cigarette (CIG) smoking in healthy adult subjects. In addition, pharmacodynamic effects (subjective effects) will be evaluated, to provide further insights on product acceptance and likelihood to use THS. Safety will be assessed throughout the study.
Summary of Results
General information about the research:
• Study Title:
Nicotine Pharmacokinetics of THS Single Use of a Regular or a Menthol Stick Compared to CIG.• 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?
Thirty-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 February 16th to April 2nd 2023.• Why was the research needed?
The research was needed to understand the nicotine pharmacokinetic profile of the Tobacco Heating System (THS), with induction heating technology, in healthy smokers following single use of THS, with a regular or menthol stick, compared to cigarette single use.• What were the main questions studied?
The study measured the amount and the time rate of nicotine uptake in blood plasma, and other parameters. These were the maximum nicotine plasma concentration [Cmax], the time to the maximum nicotine plasma concentration [Tmax], and further subsequent calculations describing the nicotine exposure profile.Who participated in the study?
Thirty-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?
Thirty participants were randomly assigned to one of six possible cross-over sequences of product use (THS, with either regular or menthol stick, and cigarette) from Day 1 to Day 3 in a confinement setting. Participants could not use any other tobacco or nicotine-containing product (TNP) other than their assigned product. From Day 1 to Day 3, after at least 23 hours of abstinence from any TNP on Day 1, and at least 24 hours after former IP use on Day 2 and on Day 3 (nicotine washout), subjects smoked a CIG or used the THS either with a regular or a menthol THS stick according to their randomized product use sequence. Blood samples were collected, at several time points after product use, from Day1 to Day 3, for determination of nicotine concentration after allocated product use. Participants were also asked, from Day 1 to Day 3, to evaluate product liking, craving for cigarettes, and their intention to use the product again. These were assessed on a scale for each evaluation. The scales went from “strong disliking” to “strong liking” for product liking; from “no craving” to “strong craving” for cigarette craving; and “very unlikely” to “very likely” for intention to use again.What medical problems (adverse reactions) did the participants have?
Overall, there were six mild adverse reactions reported in four participants. All nthe adverse reactions were mild or moderate in severity. None of these were considered related to an investigational product. There were no clinically significant findings in the physical examination, clinical laboratory, vital signs, or ECG assessments in this study.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 admission and baseline measurements on Day -1. Subjects fasted for at least 6 hours prior to the safety laboratory assessments and started abstinence of TNP. Thirty subjects were randomized to one of 6 possible full cross-over sequences of product use (THS, with either regular or menthol THS stick, and cigarette) on Day 1 to Day 3. On Day 1 to Day 3, after at least 23 hours of abstinence from any TNP on Day 1, and at least 24 hours after THS use on Day 2 and on Day 3 (nicotine washout), subjects smoked a cigarette or used the THS either with a regular or a menthol THS stick according to randomized product use sequence. Blood samples were obtained according to the standard procedures of the investigational site. Subjects were requested to report their cigarette craving, THS liking, and intention to use the THS again. After Discharge on Day 3 or after an early termination following product exposure, the subjects entered a 3-day Safety Follow-Up period during which adverse reactions reported by the subjects were collected and followed-up, concluded by telephone contact by the investigational site on the last day of the Safety Follow-Up period.What were the results of the study?
The nicotine exposure profiles and subjective effects of THS product use were assessed for THS tobacco sticks of different flavors (regular flavor; menthol flavor) and compared to those of cigarette smoking. The results of this study confirmed that nicotine exposure, from both THS Regular tobacco sticks and THS Menthol tobacco sticks, showed a lower level of nicotine uptake when using the THS Induction device compared to cigarette single use. These results are in line with historical data described for the THS device with blade heating technology.
The subjective effects of THS (induction) use were comparable to those presented in previous studies that compared THS (blade) use to cigarette use, which found that cigarette use was more satisfying while THS demonstrated comparable craving reduction. Furthermore, this study found no additional safety concerns were associated with THS 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.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: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BeqHviu0ARVnOIRMLYlD9cF8exJJ-2BKazG56uh3oI-2FqPxQ-3D-3DpL49_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI77IWlXM-2BETEVUBKY76h4JtNNsvI2wkUoJK1bXy7uS0a92CnrBsSLgkgkgf8wbUZ0hG7bhQDrhqFk3LMlwyBl4Exbvmz8ooTZ2caaHfOL78OCJQTBHy2M8m0bPx3qbB6vh5CP-2B2imAbkFdebIGfY3-2Big-2F3879uLCJeSyd0IbPBhCVEPL8ZAoKhelWAADV66dg-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cb5acf4e9b60d4defb8d608dbcfbb6813%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638332176088837462%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=45HvXC9GujFKa6ZzRZW0DOj7nHxf%2F9ecY2QBGRRSEto%3D&reserved=0REC name
HSC REC A
REC reference
23/NI/0010
Date of REC Opinion
13 Feb 2023
REC opinion
Further Information Favourable Opinion