Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1)

Abstract

IntroductionThe menthol Tobacco Heating System 2.2 (mTHS) is a newly developed candidate modified-risk tobacco product intended to reduce exposure to the harmful and potentially harmful constituents (HPHCs) of conventional cigarette (CC) smoke. This study examined the impact of switching to mTHS on biomarkers of exposure to HPHCs relative to menthol CCs (mCCs) and smoking abstinence (SA).MethodsIn this three-arm, parallel-group study, 160 Japanese adult smokers (23–65 years; smoking ≥10 mCCs per day) were randomized to mTHS (n = 78), mCC (n = 42), or SA (n = 40) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to HPHCs, human puffing topography, safety, and subjective effects of smoking measures.ResultsAfter 5 days of product use, the concentrations of carboxyhemoglobin, 3-hydroxypropylmercapturic acid, monohydroxybutenyl mercapturic acid, and S-phenylmercapturic acid were 55%, 49%, 87%, and 89% lower (p < .001), respectively, in the mTHS group than in the mCC group. Other biomarkers of exposure (measured as secondary endpoints) were 50%–94% lower in the mTHS group than in the mCC group on day 5. These reductions in the mTHS group were maintained at day 90, similar to the SA group. Switching to mTHS was associated with changes in human puffing topography (shorter puff intervals and more frequent puffs). The urge-to-smoke and smoking satisfaction levels on day 90 were similar in the mTHS and the mCC groups.ConclusionSwitching from mCCs to mTHS significantly reduced exposure to HPHCs relative to continuing smoking mCCs with concentrations similar to those observed following SA in Japanese adult smokers.ImplicationsThis randomized study compared the impact of switching to a modified-risk tobacco product candidate mTHS on biomarkers of exposure to HPHCs of cigarette smoke relative to continuing smoking cigarettes or abstaining from smoking in sequential confinement and ambulatory settings. The study showed that switching to mTHS was associated with significant biomarker reductions within 5 days in confinement, these reductions being maintained throughout the ambulatory setting up to day 90. The results provide evidence that switching to mTHS reduces real-life exposure to HPHCs in adult smokers.

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

“…In humans, previous clinical studies showed a similar nicotine absorption profile in smokers using a single Tobacco Stick or smoking a cigarette [ 16 ] and demonstrated reductions in the levels of 15 biomarkers of exposure to HPHCs in healthy adult smokers who switched exclusively to THS 2.2 for five days in confinement or for three months in ambulatory setting relative to cigarettes. The magnitude of reductions was comparable to what was observed in adult smokers who abstained from smoking [ 16 - 18 ].…”

New ideas, old problems? Heated tobacco products – a systematic review

“…Brossard et al showed that the nicotine pharmacokinetic profile of IQOS was close to that of conventional cigarettes with similar urge-tosmoke levels [36]. The use of IQOS or glo reduced the exposure to smoke toxicants in a manner comparable to quitting tobacco use [74,75]. After switching from conventional cigarettes to HTPs (IQOS or glo), a significant reduction in the levels of biomarkers of exposure to harmful and potentially harmful constituents was observed [76][77][78].…”

“…The results of in vitro and in vivo studies indicate that HTP aerosols have lower toxicity and no new hazards compared to conventional cigarette smoke [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. The results of humanbased studies also suggest that switching from conventional cigarettes to IQOS or glo leads to reductions in exposure to smoke toxicants in a manner comparable to quitting tobacco use [74][75][76][77][78]. However, there have been no independent studies regarding short-term and longterm health consequences of HTP use.…”

Effects of Switching to a Heat-Not-Burn Tobacco Product on Biologically Relevant Biomarkers to Assess a Candidate Modified Risk Tobacco Product: A Randomized Trial

“…In a series of randomized clinical trials, it has been shown that biomarkers of exposure (BoExp) to HPHCs are reduced substantially in smokers switching completely to THS after only 5 days. These changes were largely maintained in an ambulatory setting, over a period of 3 months, in Japanese and American smokers who switched to THS (12,13). In addition to favorable changes in BoExp, changes in biomarkers of effect have been shown to approach those seen in smokers who quit using tobacco products altogether (13,14).…”