Evaluation of Biological and Functional Changes in Healthy Smokers Switching to the Tobacco Heating System 2.2 Versus Continued Tobacco Smoking: Protocol for a Randomized, Controlled, Multicenter Study

S Michael Ansari, Nicola Lama, Nicolas Blanc, Marija Bosilkovska, Andrea Donelli, Patrick Picavet, Gizelle Baker, Christelle Haziza, Frank Lüdicke, S Michael Ansari, Nicola Lama, Nicolas Blanc, Marija Bosilkovska, Andrea Donelli, Patrick Picavet, Gizelle Baker, Christelle Haziza, Frank Lüdicke

Abstract

Background: Tobacco harm reduction, substituting less harmful tobacco products for combustible cigarettes, is a complementary approach for smokers who would otherwise continue to smoke. The Philip Morris International (PMI) Tobacco Heating System (THS) 2.2 is a novel tobacco product with the potential to reduce the risk of harm in smokers compared to continued smoking of combustible cigarettes. It heats tobacco electrically in a controlled manner, never allowing the temperature to exceed 350°C, thereby preventing the combustion process from taking place and producing substantially lower levels of toxicants while providing nicotine, taste, ritual, and a sensory experience that closely parallels combustible cigarettes. Previous clinical studies have demonstrated reduced exposure to the toxicants (approaching the levels observed after quitting) for smokers who switched to THS 2.2, for three months. For adult smokers who would otherwise continue smoking combustible cigarettes, switching to THS 2.2 may represent an alternative way to reduce the risk of tobacco-related diseases.

Objective: This study aimed to further substantiate the harm reduction potential of THS 2.2 by demonstrating favorable changes in a set of 8 coprimary endpoints, representative of pathomechanistic pathways (ie, inflammation, oxidative stress, lipid metabolism, respiratory function, and genotoxicity), linked to smoking-related diseases, in smokers switching from combustible cigarettes to THS 2.2.

Methods: This study was a randomized, controlled, two-arm parallel group, multicenter ambulatory US study conducted in healthy adult smokers switching from combustible cigarettes to THS 2.2 compared with smokers continuing to smoke combustible cigarettes for six months. Subjects had a smoking history of at least ten years and did not intend to quit within the next six months.

Results: Enrollment started in March 2015 and the trial was completed in September 2016. In total, 984 subjects were randomized (combustible cigarettes, n=483; THS 2.2, n=477), and 803 completed the study. The results are expected to be available in a subsequent publication in 2019.

Conclusions: In this paper, we describe the rationale and design for this clinical study that focused on the evaluation of THS 2.2's potential to reduce the risk of smoking-related diseases compared with that of combustible cigarettes. This study will provide insights regarding favorable changes in biological and functional endpoints informed by effects known to be seen upon smoking cessation.

Trial registration: ClinicalTrials.gov NCT02396381; https://ichgcp.net/clinical-trials-registry/NCT02396381 (Archived by WebCite at http://www.webcitation.org/71PCRdagP).

Registered report identifier: RR1-10.2196/11294.

Keywords: biomarkers; harm reduction; heated tobacco; metabolic networks; pathways; risk; smoking; smoking cessation; tobacco; tobacco products.

Conflict of interest statement

Conflicts of Interest: The work reported in this publication involved a candidate MRTP developed by PMI Research & Development. All authors are (or were) employees of PMI or worked for PMI under contractual agreements. PMI is the sole source of funding and sponsor of this project.

©S Michael Ansari, Nicola Lama, Nicolas Blanc, Marija Bosilkovska, Andrea Donelli, Patrick Picavet, Gizelle Baker, Christelle Haziza, Frank Lüdicke. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 24.08.2018.

Figures

Figure 1
Figure 1
Design of the study. Eligible subjects were provided with the Tobacco Heating System 2.2 (THS 2.2) at visit 3 (V3) and were allowed to use the product freely during the 6- to 10-day run-in period until V4. Those willing to use THS 2.2 exclusively during the study were randomized to the THS 2.2 or cigarette arms.
Figure 2
Figure 2
Flow chart of study participants. Asterisk indicates sites terminated due to noncompliance with Good Clinical Practice (GCP). CC: combustible cigarette; THS 2.2: Tobacco Heating System 2.2.

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