Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2017 Aug 22;17(1):673.
doi: 10.1186/s12889-017-4678-9.

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

Nathan Gale  1 , Mike McEwan  1 , Alison C Eldridge  1 , Neil Sherwood  2 , Edward Bowen  3 , Simon McDermott  4 , Emma Holmes  4 , Andrew Hedge  4 , Stuart Hossack  4 , Oscar M Camacho  1 , Graham Errington  1 , John McAughey  1 , James Murphy  1 , Chuan Liu  1 , Christopher J Proctor  1 , Ian M Fearon  5
Affiliations
Randomized Controlled Trial

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

Nathan Gale et al. BMC Public Health. .

Abstract

Background: Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP).

Design and methods: This study will assess biomarkers of exposure in current smokers who either remain smoking, switch to THP use, or quit all tobacco use completely, for 5 days. The study is an in-clinic (confinement) two-centre, randomised controlled clinical study with a forced-switching design. Subjects of either gender will be aged 23-55 years (minimum legal smoking age plus 3 years), of Japanese origin and with a verified smoking status (assessed by exhaled breath carbon monoxide and urinary cotinine levels). Subjects will have a usual brand cigarette within the International Organisation for Standardisation (ISO) tar band of 6-8 mg and will be judged to be healthy by medical history, physical examination, vital signs, electrocardiography (ECG), clinical biochemistry and lung function tests. The primary objective of this study is to assess changes within groups in selected biomarkers of exposure (BoE) and of biological effect (BoBE) after a forced switch from a commercial control cigarette to either a menthol or a non-menthol THP. Secondary objectives are to assess between-group differences, to determine nicotine pharmacokinetics for cigarettes and THPs, to assess subject's satisfaction with the study products, and to monitor additional endpoints related to safety and product use.

Discussion: Data from this study will advance our scientific understanding of the changes in exposure to cigarette smoke toxicants in smokers who switch to using a THP.

Trial registrations: UMIN000024988 (25th November 2016); ISRCTN14301360 (14th December 2016).

Keywords: Biomarker of exposure; Harm reduction; Smoking; Tobacco heating product.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study will be conducted in compliance with the ethical principles of the Declaration of Helsinki, Good Clinical Practice (International Conference on Harmonisation (ICH) E6 Consolidated Guidance, April 1996) and Japanese law. The protocol (Version 2.0 dated 17th November 2016) and the informed consent forms (Additional file 1: Appendix 1) were submitted for review to the Hakata Clinic Institutional Review Board (IRB), Medical Co. LTA, Fukuoka, Japan. A favourable opinion from the IRB was obtained on 16th December 2016. All substantial protocol amendments will be approved by the IRB responsible for the study and the IRB will be informed of minor amendments to the protocol which do not require their approval.

The Principal Investigator (PI) will ensure that participants are given full and adequate oral and written information in non-technical terms about the nature, purpose, potential risks and any possible benefits of study participation. Participants will be given time to consider all the information, the opportunity to ask questions and will be required to read, sign and date informed consent forms (ICFs) that summarise the discussion before participating in any procedures related to the study.

Consent for publication

Not applicable, our manuscript does not contain data from any individual person.

Competing interests

This study will be funded by British American Tobacco (Investments) Limited. NG, MMcE, AE, OMC, GE, JMcA, JM, CL, CJP and IMF are current employees of British American Tobacco (Investments) Limited. NS is a consultant employed by BAT to provide consultancy services for this study. EB, SMcD, AH, SH and EH are employees of Covance Clinical Research Unit Limited, a CRO contracted to provide numerous services to the study. The PI is an employee of Medical Co. LTA, a CRO contracted by the Sponsor to provide clinical conduct services for the study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Outline of study procedures
See this image and copyright information in PMC

References

    1. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. 2009;49:57–71. doi: 10.1146/annurev.pharmtox.48.113006.094742. - DOI - PMC - PubMed
    1. Blaszkewicz M, Liesenhoff-Henze K. Creatinine in urine [Biomonitoring Methods, 2010]. In: Deutsche Forschungsgemeinschaft, editors. The MAK Collection for Occupational Health and Safety. Weinheim: Wiley-VCH Verlag GmbH; 2012. p. 169–84.
    1. Digard H, Proctor C, Kulasekaran A, Malmqvist U, Richter A. Determination of nicotine absorption from multiple tobacco products and nicotine gum. Nicotine Tob Res. 2013;15(1):255–261. doi: 10.1093/ntr/nts123. - DOI - PMC - PubMed
    1. Dittrich DJ, Fieblekorn RT, Bevan MJ, Rushforth D, Murphy JJ, Ashley M, McAdam KG, Liu C, Proctor CJ. Approaches for the design of reduced toxicant emission cigarettes. Spring. 2014;3:374. doi: 10.1186/2193-1801-3-374. - DOI - PMC - PubMed
    1. Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors. Br Med J. 1994;309(6959):901–911. doi: 10.1136/bmj.309.6959.901. - DOI - PMC - PubMed

Publication types

LinkOut - more resources