Nicotine uptake Not Applicable
Conditions
Interventions
Subjects will be randomly assigned to one of ten sequences and use each of the following five investigational products once in accordance with the assigned sequence.
Test products:
1. Nordic Spirit c
Sponsors
JT International SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give written informed consent for participation in the study 2. Healthy male or female subject aged 19-64 years inclusive 3. Body Mass Index (BMI) =18.5 and =30.0 kg/m² at screening 4. Subject who currently use factory-made Swedish portion snus (nicotine content =8 mg per pouch) daily (=1 snus pouch per day, 7 days per week) and who indicate that they have used such snus continuously for at least six months prior to screening 5. Positive urine cotinine test (>200 ng/ml) at screening 6. Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator 7. 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], IUD or IUS. Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject
Exclusion criteria
Exclusion criteria: 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 visit for the outcomes assessments 3. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma 4. Any surgery within 6 months of the screening visit that could negatively impact on the subject's participation, as judged by the Investigator 5. Any planned major surgery within the duration of the study 6. Medical history of seizures (single occasions of febrile seizure in the childhood excluded) 7. Clinically significant liver disease, as judged by the Investigator, and/or an elevation in total bilirubin, alkaline phosphatase, LDH, AST, or ALT of >3 times the upper limit 8. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C virus antibodies and HIV 9. Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to any use of the IP 10. Systolic blood pressure of =140 mmHg or diastolic blood pressure of =90 mmHg, after 10 min supine rest 11. Poor peripheral venous access, as judged by the Investigator 12. Female subjects who are pregnant or who are currently breastfeeding 13. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator 14. Presence or history of drug abuse and/or anabolic steroids, as judged by the Investigator 15. Subjects who have used any tobacco/nicotine-containing products (including electronic cigarettes, heat-not-burn products, nicotine pouches etc) or NRT medications, other than factory-made Swedish portion snus within 14 days of screening. (A single occasional use of conventional cigarettes within the 14 days prior to screening is allowed) 16. Subjects who, prior to enrolment, are planning to quit tobacco use during the study period or are postponing a quit attempt in order to participate in the study. All subjects will be informed that they are free to quit tobacco use and withdraw from the study at any time 17. Any use of prescription or over-the-counter bronchodilator medication (e.g. inhaled or oral ß-adrenergic agonists) to treat a chronic condition within the 12 months prior to the first visit for the outcomes assessments 18. Any medication (prescription or over-the-counter [OTC]) within 14 days or within 5 half-lives of the drug (whichever was longer) prior to the first visit for the outcomes assessments, which has an impact on CYP2A6 activity 19. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening 20. Planned treatment or treatment with another investigational product within 3 months prior to the first visit for the outcomes assessments. Subjects consented and screened but not dosed in previous phase I studies are not excluded 21. Subjects who are employed by the tobacco industry, the clinical site, or handle unprocessed tobacco as part of their job 22. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma nicotine levels will be analyzed for the pharmacokinetic parameters (maximum plasma concentration [Cmax], time to Cmax [Tmax], area under the concentration versus time curve from time point zero to time point 60 minutes [AUC0-60] and AUC from time zero to the last time point with a measurable concentration [AUC0-last] following a single use) using blood samples which will be collected up to 10 minutes before investigational product use and at 5, 8, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours after the start of investigational product use. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Changes in vital signs (blood pressure and pulse rate) from the baseline will be measured at 5, 30 and 60 minutes after the start of investigational product use 2. Subjective effects (including satisfaction, psychological reward, aversion and relief) will be measured using a modified version of the Product Evaluation Scale following a single use of the investigational product 3. Intent to use the product again will be measured using the Intent to Use the Product Again Questionnaire (visual analogue scale) following a single use of investigational products 4. The amount of nicotine delivered from Nordic Spirit products 6 mg, 9 mg and 11.2 mg and conventional Swedish portion snus will be measured following a single use of investigational products. The difference between the nicotine content of the unused/reference pouch and the pouch used in the study will be used to calculate the delivered amount of nicotine | — |
Countries
Sweden
Outcome results
None listed