Clinical studies

Laboratory tests are invaluable in helping us assess the safety of our products, but to fully substantiate their reduced risk potential, it is crucial that we understand the biological impact they have on humans.

To assess the potential effects of our products, we conduct extensive laboratory tests to evaluate their safety and performance. Much can be learned from chemical, physical and toxicology assessments, and we are doing everything we can to use models that mimic the human body and push the sensitivity of our tests.

 

Evaluating biological impact

Clinical studies using human subjects remain the gold standard for evaluating how people use a product and the biological consequences of doing so and are important for us to assess the reduced risk potential of products intended to present lower risks than cigarettes.

One of these tests, a pharmacokinetic (or PK) study, examines how quickly nicotine is taken from a product into the bloodstream. Although by no means the only factor involved, this can be crucial in determining whether a new product could be an adequate alternative for a smoker.

Laboratory analytical studies can determine what levels of toxicants are found in the emissions of new products, but human exposure will depend both on these emissions and how the products are used.

Evaluating biological impact

 
Biomarkers

Biomarkers

When a chemical is taken into the body, it or its metabolic by-products can be measured in the blood, breath, saliva or urine. These biomarkers of exposure (BoEs) indicate how much of a particular substance has been taken into the body. Generally, the higher the levels found, the greater the exposure of the person to the original chemical. By comparing levels of BoEs when a person smokes cigarettes with those seen after they’ve switched to using a vapour product or tobacco heating product (THP), we can determine whether and to what extent use of the alternative product changes the amount of toxic chemicals or nicotine entering the body. In line with the US Institute of Medicine’s opinion that for a product to be considered a reduced harm product a consumer’s biological responses to using it should be similar to those of a former smoker1, we also compare BoE levels of consumers using potentially reduced risk products with those in people who have quit smoking.

To assess the effects that chemicals have when inside the body, we can measure other indicators produced by the body in response to their presence. These indicators, called biomarkers of biological effect (BoBE), may be suggestive of early changes that could lead to disease development. We have identified BoBEs implicated in key processes (for example, inflammation and oxidative stress) that contribute to the development and progression of smoking-related diseases, such as cardiovascular disease and chronic obstructive pulmonary disease. Comparing BoBE levels can tell us whether switching from cigarettes to a novel product or quitting is likely to change the risk of developing a smoking-related disease.

 

PK studies on vapour

By examining how much nicotine a product delivers and how quickly it reaches the consumer’s bloodstream, a PK study can provide a preliminary indication of whether a product is likely to be acceptable to a smoker.

To evaluate how effective our Vype vapour products are at delivering nicotine, we conducted a clinical PK study to assess the nicotine delivery from different variants of Vype ePen products compared to a commercially available cigarette in healthy participants. The study was conducted in Merthyr Tydfil, Wales, by Simbec Research Limited. The scope of this study aimed to investigate the effect of nicotine salt, effect of nicotine concentration, and effect of device (technology) compared to a combustible cigarette.

Participants were experienced vapers that occasionally smoked cigarettes (dual users). Participants were confined in the clinic for 8 days and on each day, according to a randomisation programme, they were assigned a specific product. In brief, participants used the study products for 5 minutes and blood samples were collected at predetermined intervals for 120 minutes to track the nicotine concentration. For full details of the study design, we have registered the study in an open-access database (read more here ISRCTN55307091 ).

Our results show that Vype ePen 3, with high nicotine concentration delivers, nicotine similar to a combustible cigarette. Our results also show that nicotine salt drives better nicotine delivery. Lastly, Vype ePen 3, which has a better wick technology and higher nicotine per puff than ePen 2, had a significantly better nicotine delivery compared to its predecessor. "Results from this clinical study suggests that Vype ePen 3, particularly the vPro range, is a truly innovative product and a leading performing pod-mod system that can deliver nicotine as efficiently as a combustible cigarette", says Dr Mike McEwan, Senior Clinical Scientist.

PK studies on vapour

 

Clinical studies on Tobacco Heating Products

Clinical studies on tobacco heating products

To evaluate a person’s exposure to toxic smoke constituents when using our THP product glo, we conducted a clinical study in Japan to assess a wide range of BoEs before and after switching from cigarettes to glo for five days3. Results showed that after smokers switched, their exposure to toxic smoke constituents was substantially reduced4. "Some of the decreases we observed in participants switching to glo were broadly equivalent to quitting smoking," says Nathan Gale, who was the study lead. "This suggests that glo has the potential to be a reduced exposure and/or risk product, but further studies are needed to determine whether these reductions are sustained and translate to a reduction in smoking-related health risks."

Consumers in different countries can vary in terms of both behaviour and genetic variability, so we have carried out a similar study in the UK, examining BoEs before and after switching from cigarettes to glo or a vapour product (ISRCTN80651909 ), the results are currently being analysed. We are currently working on our biggest and most complex potentially reduced risk product clinical study to date, examining BoBEs (indicators of risk) in smokers who continue smoking, switch to using glo or quit nicotine and tobacco product use completely. This study will help us determine how switching for one year impacts indicators that might be related to people’s long-term health risks.

References

  1. Institute of Medicine (2012).

    Scientific Standards for Studies on Modified Risk Tobacco Products. Washington, DC: The National Academies Press.

  2. Fearon et al. (2017).

    E-cigarette nicotine delivery: data and learnings from pharmacokinetic studies.  Am J Health Behav 41: 16–32.

  3. Gale et al. (2017).

    A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product. BMC Public Health 17: 673.

  4. Gale et al (2018).

    Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects Nicotine & Tobacco Research.

 
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