E-cigarette Nicotine Pharmacokinetic Study

Inclusion Criteria

• •1. Prior to study start, subjects must be current smokers of conventional factory-made cigarettes (eCO \>10ppm at screening) who have either tried or are occasional users of e-cigarettes. Subjects must be smoking ≥10 cigarettes per day and must have done so for at least one year. Smoking status will be confirmed with a urinary cotinine level of ≥200ng/ml (determined using NicAlert cotinine test kit) and an exhaled breath CO level of \>10ppm (determined using a Smokerlyzer breath CO monitor) at screening, as well as by tobacco use questionnaire.
• •2. Subjects will be males or non-pregnant, non-lactating females, and between 22 and 55 years of age inclusive. Age verification will be performed by checking of Federal or state-issued ID (eg. passport or driving licence) during screening.
• •3. Women of child-bearing potential should be using one of the following acceptable methods of contraception : combined (oestrogen and progestogen containing) oral, intravaginal or transdermal hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception, either oral, injected or implanted, associated with inhibition of ovulation; progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide.
• •4. Women of non-childbearing potential may be included if they are either surgically sterile (hysterectomy and/or oophorectomy) or postmenopausal for more than 1 year and must have a negative urine pregnancy test result during screening. Women who are surgically sterile must provide documentation of the procedure by an operative report.
• •5. Male subjects must use an approved method of birth control during the entire study. These subjects must not donate sperm during this time.
• •6. Subjects must be in good health, as judged by the PI or the appropriately qualified designee based on medical history, ECG, vital signs, blood biochemistry, haematology, urinalysis and physical examination.
• •7. Subjects must have a body mass index (BMI) between 18 and 30 kg/m2 inclusive. Male subjects must have a weight between 60 and 120kg and female subjects between 50 and 100kg.
• •8. No clinically significant abnormalities in blood pressure values.
• •9. Subjects will have negative results for the urinary drug of abuse screening and alcohol test.
• •10. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.
• •To be confirmed during each clinic visit:
• •1\. Abstinence from tobacco and nicotine products will be confirmed by an exhaled breath CO reading \<15ppm.
• •11. Subjects who have used any drugs or substances (except tobacco) known to be strong inducers or inhibitors of any CYP enzymes (formerly known as cytochrome P450 enzymes) within a 28 days period prior to first product administration. For a list of such drugs and substances, please refer to http://medicine.iupui.edu/clinpharm/ddis/main-table/.
• •12. Subjects who have had any treatment with smoking cessation medications (e.g. Bupropion, Chantix or any NRT) within 30 days of the planned first product use occasion.
• •13. Subjects with any other clinically significant medical history, in the Investigator's opinion, including conditions which might affect drug absorption, metabolism or excretion.
• •14. Female subjects, who are pregnant or become pregnant during the course of the study.
• •15. Subjects who have lost or donated more than 450ml of blood within the 2 months preceding the first product administration.
• •16. Subjects who are self-reported non-inhalers (smokers who draw smoke from the cigarette into the mouth and throat but who do not inhale). Subjects who are observed as non-inhalers at Admission by the clinic staff will be excluded.
• •17. Subjects who are currently trying to stop smoking or to stop using e-cigarettes, or considering stopping in the next two months. All subjects will be informed that they are free to quit smoking/using e-cigarettes and withdraw from the study at any time.
• •18. Subjects who are unwilling or unable to comply with the study requirements.
• •19. Subjects who in the opinion of the Principal Investigator or their appropriately qualified designee should not participate in the study for any other reason.
• •To be re-confirmed during each clinic visit: