A single-dose, randomised, crossover study to assess the nicotine pharmacokinetics of oral nicotine products in healthy adult users of smokeless pouch products
- Conditions
- icotine uptake in harm reduction productsNot Applicable
- Registration Number
- ISRCTN12265853
- Lead Sponsor
- British American Tobacco (United Kingdom)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 53
1. Willing and able to give written informed consent for participation in the study
2. Healthy male and female subjects aged 19-55 years inclusive
3. Body Mass Index (BMI) = 18.5 and = 30.0 kg/m2 and a minimum weight of =45 kg (females) or =52 kg (males)
4. Clinically normal medical history, physical findings, vital signs, electrocardiogram (ECG) and laboratory values at the time of screening, as judged by the Investigator. No abnormal results judged by the Investigator as clinically significant are allowed.
5. Daily snus and/or nicotine pouch user who must have used pouched products for at least 12 months and who use these pouch products under their upper lip. Subjects who use pouched snus and/or nicotine pouches should typically use at least five pouches per day, with pouch weights of 0.6 g or above. Subjects should be willing and able to use products with nicotine content =15 mg/g.
6. Stated willingness to abstain from nicotine and tobacco products (except for the IPs provided) from 12 hours prior to each study product administration until the end of each PK sampling
7. Successful completion of the product familiarisation session for study product use prior to the first study product administration (the subject is able to follow the instructions, can tolerate the product and does not experience any adverse effects different from what is expected from typical smokeless pouch use during the training session).
8. Positive urine cotinine test (=200 ng/ml) at screening and at Day -1
9. Women of childbearing potential (WOCBP) must be willing to use a sufficient contraceptive method for the duration of the study, this includes mechanical barrier (e.g., a male condom or a female diaphragm), combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal anticonception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD) or intrauterine system (IUS). Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject.
Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle-stimulating hormone [FSH] 25-140 IE/l is confirmatory).
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study
2. Any clinically significant illness, medical/surgical procedure or trauma within 2 weeks of the first administration of IP
3. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma
4. Any planned major surgery within the duration of the study
5. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV)
6. After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
6.1. Systolic blood pressure <90 or >140 mmHg, or
6.2. Diastolic blood pressure <50 or >90 mmHg, or
6.3. Pulse <40 or >90 bpm
7. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator
8. Presence of braces, partials, dentures or any dental work that could, in the opinion of an Investigator, affect the conduct of the study (including missing molars)
9. Presence or history of significant form of oral and/or pharyngeal inflammation, oral lesions and/or gum disease or temporomandibular joint dysfunction
10. Existing signs of skin irritation or skin damage at the sites where the Equivital LifeMonitor device is to be located, as judged by the Investigator
11. Subjects with implanted defibrillators or pacemakers
12. Female subject who is pregnant or lactating
13. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to nicotine
14. Plan to quit using tobacco- or nicotine-containing products within 3 months of the end of the current study, or previously attempted to quit using tobacco- or nicotine-containing products in the 28 days prior to the first IP use
15. Planned treatment or treatment with an investigational medicinal product or another IP within 3 months prior to Day -1. Subjects consented and screened but not dosed in previous phase I studies are not excluded.
16. Positive screening result for drugs of abuse or alcohol at the time of screening or on admission to the unit prior to first use of IP. Positive results that are expected given the subject’s medical history and prescribed medications can be disregarded as judged by the Investigator.
17. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator
18. Presence or history of drug abuse, as judged by the Investigator
19. History of, or current use of, anabolic steroids
20. Plasma or platelet donation within one month of the first IP use or blood donation (or corresponding blood loss, =450 mL) during the three months prior to the first IP use
21. Employees or immediate relatives of the tobacco industry or the clinical site
22. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Plasma nicotine maximum plasma concentration (Cmax), time to Cmax (Tmax) and area under the plasma concentration versus time curve 0 to 240 minutes (AUC0-240), analysed after collection of blood samples at pre-use, 5, 7, 10, 15, 20, 25, 30, 35, 40 min, 1 hour, 2 hours and 4 hours.
- Secondary Outcome Measures
Name Time Method 1. Overall product liking (OPL) and intent to use again (IUA) assessed with questionnaires using a visual analogue scale (VAS) (0-100 mm) at 4 hour post product use<br>2. Amount mg/unit and extracted fraction (%) of nicotine, sweeteners and major flavour components measured using saliva samples at 4 hours post product use